Protein deficiency, energy deficiency, and the oedema of malnutrition

The role of dietary protein deficiency in kwashiorkor is uncertain, although it has been shown not to be involved in the famine oedema of adults. A study of six different diets given to 103 children with oedematous malnutrition showed that the rate of loss of oedema was strongly correlated with the dietary energy intake (r=-0.75) but not with the protein intake (r=0.03). 66 patients given a very-low protein diet (2.5 percent protein energy) lost oedema as fast as those given five times as much protein. The energy intake above which oedema accumulated was 245-270 KJ/kg/day. Because energy deficiency is not invariably associated with oedema it cannot be the only factor involved, and the other necessary dietary component(s) must therefore have been present in surfeit in all the therapeutic diets. This could be potassium together with factors necessary for its retention. The accessory ingredients must be low in foods associated with human and experimental nutritional oedema. It is suggested that protein deficiency is not the cause of the oedema of kwashiorkor and that there is no need to postulate a different pathogenesis for this oedema from starvation oedema of adults. (Summary)

Research in Jamaica with particular reference to nutrition

The argument is developed that, because the problems faced in the Third World are different from those of the technologically advanced countries, the problems of the Third World are not being addressed in sufficient impact. The blind transfer of skills and techniques and training curricula exacerbates rather than helps us to face the unsolved questions that cripple much of the Third World. The way forward is to establish and strengthen existing centres of indigenous science and to bring them to a level of sophistication that is comparable with those in technologically developed societies. The principles involed are illustrated by considering human nutrition. The problems are of staggering proportions, with about one third of the world's children chronically undernutritioned. The resultant stunting of mental and physical development in such a large proportion of the world's children, and the adults into which they mature, is clearly an important problem. And yet, the extant expertise to tackle these problems at the most fundamental levels is very limited. It is an absolute truth that you cannot apply what you do not know! The most exclusive encouragement of "applied" or "health services" research, posited upon animal work in First World institutions is clearly unbalanced. I have tried to start to answer why Third World science is a cinderella in this paper: the reasons are clearly both very complex and not understood by those who try to help the Third World from abroad or by those who control the resources with the Third World. (AU)

Leukocyte electrolytes and sodium transport in protein energy malnutrition

Intracellular electrolytes and sodium transport were measured in leukocytes obtained from malnourished children. In the presence of edema, leukocyte sodium and potassium were raised. The total flux and the glycoside-sensitive portion were increased. Loss of edema was associated with reductions in all these measurements. In marasmus, glycoside-sensitive sodium efflux was reduced compared to recovered values. Sodium was increased and potassium reduced. It is concluded that at least two defects in sodium transport may occur in protein energy malnutrition, an increased passive permeability in kwashiorkor and a reduced active transport for sodium in marasmus. (AU)

Zinc and muscle growth during recovery from malnutrition - abstract

During recovery from severe malnutrition, muscle gain is slow relative to overall weight gain. We postulated that this might be due to an inadequate supply of zinc. We therefore compared nitrogen (N) balance and protein synthesis rates (as estimates of muscle gain) during early, mid and late recovery in children fed 3 different levels of dietary zinc (Low Zn gp.n = 4; Moderate Zn gp.n = 4; High Zn gp.n = 3). N intake was similar in the 3 Zn groups throughout recovery. N net absorption and N retention were also similar in early recovery. Later, both increased in the moderate and high Zn groups only: so also did the N retention /g wt gained. By late recovery, they were each significantly higher in the high Zn gp than in the low Zn gp. Thus, Zn supplementation of the relatively low Zn recovery diet resulted in synthesis of tissue richer in N - and therefore, by implication, having a higher proportion of muscle. Protein synthesis rates were calculated from the 15N enrichments of urinary urea and ammonia at plateau, obtained during a constant nasogastric infusion of 15N labeled glycine. Overall, the results using the 2 different end products were not different. However, there was a difference among the Zn gps in the 15N ammonia enrichments. From these values, protein synthesis rates were significantly higher than in the high Zn gp than in the low Zn gp by late recovery (table included). These data are consistent with the N balance data in that they indicate increased muscle protein metabolism with Zn supplementation (AU)

Glutathione in malnutrition - abstract

Malnourished children are exposed to increased oxidative stress because of associated infections, diarrhoea and contaminated feeds. Plasma levels of vitamin E, the most abundant naturally-occurring antioxidant,are low in severely malnourished children. One would therefore expect that the increased oxidant stress and decreased protection could lead to oxidative damage in the malnourished child (Table Included). Glutathione (GSH) has a central role in the antioxidant system and increased oxidant stress is reflected in low glutathione concentratioins. GSH is essential for the activities of glutathione peroxidase and glutathione S-transferase and at low levels cell damage occurs. We have therefore measured GSH levels in the red cells of severely malnourished children in order to assess this central part of the cellular antioxidant machinery. Total and oxidased glutathioine (GSSG) were measured on admission in 93 severely malnourished children. In 49 of theses children, both parameters were again measured at discharge. Forty healthy children acted as controls. SH returned to normal levels in the oedematous groups. It is concluded that red cell GSH is significantly reduced in oedematous malnutrition. This may be one of the factors associated with the different clinical presentatioins of oedematous and non-oedematous malnutrtion (AU)

Increased urinary output of mercapture acids in severely malnourished children - abstract

Mercapturic acids (MA) are a group of compounds produced during detoxification processes in vivo. The extent to which a cell is exposed to toxic substances is therefore reflected by increased urinary. MA output. Toxins are effectively neutralised by the formation of a conjugate with glutathione (GSH); this reaction is catalysed by glutathione s-transferase (GST). Severely malnourished children have poorly functioning antioxidant systems and are often exposed to increased oxidant stress; their detoxification systems are probably being overworked. This is supported by our previous finding that erythrocyte GST activity is induced in malnourished children. As MA are the end product of GST activity, we reasoned that hte urinary MA output should also be elevated. This may assist in explaining the low level of GSH foun in children with oedematous malnutrition and provide a quantitative measure of the total body load of exogenous and endogenous carbony-like toxins. Twenty -four-hour urinary output of MA and creatinine were measured in 19 severely malnourished children, on admission and at discharge. Three healthy children served as controls. The results are as follows: MA (æmol/kg child) Control - 1.2ñ0.1, Malnour - 4.2ñ0.6, Maras. - 3.4ñ0.8, Mar/Kwash. - 5.1ñ1.2, Kwash. 4.4ñ1.1 . MA (æmol/mmol creat) Control - 5.8ñ0.9, Malnour. - 37.3ñ5.7, Maras. - 26.0ñ7.1, Mar/Kwash. - 57.3ñ13.0, Kwah. - 32.6ñ7.3. The MA levels were maintained at discharge. Creatinine levels on admission were significantly lower than normal, they were increased at discharged. We conclude that the urinary MA output of severely malnourished children is significantly higher than normal; this is probably indicative of their burden of toxins. The high MA output at discharge is possibly as a result of oxidant stress imposed by the high polyunsaturated fat content of the recovery diet (AU)

Zinc and copper nutriture in and during recovery from severe malnutrition - abstract

Interrelationships between zinc and copper have been demonstrated in rats and in adult humans. In rats, serum concentrations correlate negatively, and in both, zinc inhibits copper absorption. In order to study these phenomena in malnourished infants, we first measured plasma zinc and copper concentrations in plasma on admission. Later, we observed the effect of different dietary zinc intakes on copper absorption and on plasma zinc and copper in 11 recovering children. On admission, 7 out of 20 children had both low plasma zinc and copper concentrations. Six of these had oedema and 2 died. The 8 marasmic children had a mean plasma zinc of 12.9 æmol/L and plasma copper of 21.4 æmol/L. The 12 oedimatous children had a mean plasma zinc of 10.1 æmol/L and plasma copper of 11.6 æmol/L. There was no relationship between plasma zinc and copper values. The children with most oedema had the lowest plasma copper concentrations. The recovering children were fed a high energy diet containing 18 æmol copper/L from soya and either 52 (n=4), 126 (n=4) or 196 (n=3) æmol zinc/L. Their plasma zinc concentrations fell, most in the low zinc group and least in the high zinc group. Simultaneously, their plasma copper concentrations rose. Overall, the change in plasma zinc correlated positively with the change in plasma copper (r = 0.72, p < 0.05). The low zinc group had a very small nett zinc absorption throughout recovery: their nett copper absorption remained high. Copper intake correlated positively with faecal output (r = 0.88, p < 0.001) and this relationship did not differ among the 3 zinc groups. Thus, in malnourished infants there was no relationship between plasma zinc and copper. During their recovery, though, there was a relationship between the changes in these values, there was no effect of zinc supplementation on total plasma copper or on nett copper absorption from this soya diet. This work was supported by the Wellcome Trust (MHG) and the M. R. C. (BEG)

Magnesium chloride induced acidosis in malnutrition - abstract

Because their is a total body deficit of magnesium in malnutrition, magenesium salts are routinely prescribed in treatment. Several children were observed to develop severe hyperchloraemic acidosis after admission to the ward, and urine from recovering children was found to be highly acidic. This study tested the hypothesis that the acidosis was iatrogenically induced by the magnesium chloride supplement. Six malnourished and 5 recovering children were treated in the standard way except that they were given magnesium chloride (1 mmol/kg/d) for 4 days and then magnesium acetate for 4 days. The order of the salts was changed in alternate children. Jugular venous Astrup and timed urine collections were made at the end of each period. The malnourished children developed sytemic acidosis on the magnesium chloride supplement (pH 7.3 ñ 0.01 vs - #.6 ñ 1.1). Those children who were given the acetate salt first remained in acid-base equilibrium whereas those who were given the chloride first had not regained normal acid base status after 4 days on the acetate. On the chloride salt the urinary pH was lower (5.0 ñ 0.3 vs 6.5 ñ 0.3), the titratable acidity higher (1.5 ñ 0.2 vs 0.4 ñ 0.3 æEq/min) and the total acid (TA = ammonia - HCO3) output higher (5.5 ñ 0.8 vs 2.1 ñ 0.4 æEq/min), than on the acetate salt. The recovering children also developed a mild systemic acidosis on the chloride (Base excess - 5.5 ñ 0.9 vs 2.3 ñ 0.5) and excreted a highly acid urine, pH 4.8 ñ 0.1; on the acetate the urine was also acid pH 5.1 ñ 0.1. The total acidity output was 20.4 ñ 1.1 æEq/min on the chloride and 15.3 ñ 1.4æEq/min on the acetate. It is concluded that magnesium chloride is the cause of the iatrogenic systemic acidosis seen in our malnourished children. Whilst malnourished they excrete a maximally acid urine, however the total acid output is small and leads to a progressively positive hydrogen ion balance, which the child cannot correct within four days of ceasing the chloride load. This work was supported by the Wellcome Trust (AU)

The excretion of taurine in severe malnutrition - abstract

Taurine may be a conditionally essential nutrient in man. Diets lacking taurine have resulted in reduced body and urinary taurine and in the development of abnormal retinograms, which were reserved with taurine supplementation. Malnourished children are often fed diets low in taurine and other sulphur amino acids, particularly cow's milk-based diets. It is therefore possible that their taurine body pools and hence excretion are low. Urinary taurine was measured, by spectrophotometry, in 37 malnourished children, aged 3-24 months, on admission to hospital and when recovered. Four normals, aged 60-96 months, were also studied. Taurine in the urine of the normals, expressed as uM/d, was about 6 times that of the malnourished children on admission and on discharge respectively. The difference was even greater when expressed per body weight. The values were also low when compared with published values for normals. The children were rehabilitated on a cow's milk-based diet. Thus, the over-all low levels most likely resulted from low dietary taurine and reduced synthesis. Urinary taurine can serve as a crude index of taurine status, suggesting that the children were at risk of developing abnormal retinograms. The lowest values were from the oedematous children. This observation could be important in terms of new data showing that taurine protects cell membranes by attenuating toxic compounds. Taurine supplementation might beneficial in severe malnutrition (AU)

Zinc absorption in malnutrition - abstract

Malnourished children are often zinc-deficient. Net intestinal absorption (NA) of zinc is the main factor controlling zinc status: NA = TA - ES, where TA is total intestinal absorption, and ES is endogenous secretion of zinc into the intestine. In order to investigate factors affecting zinc homeostasis, we have measured NA and TA in 7 severely malnourished and in 10 recovered (weight-for-height) children, 8 to 18-months-old. NA was calculated as the difference between feed zinc intake and faecal zinc output over a 3-day period. TA was calculated as the difference between feed intake and faecal output of the stable isotope, 70Zn, given over the first 6 hours of the balance. Eight of the recovered children, the control group, were given a standard cow's milk-based infant formula at 'maintenance energy' intake. TA of zinc was 25ñ7 percent of zinc intake (meanñSD); it increased significantly with the age and weight of the child, and insignificantly with the weight gain (RWG). NA of zinc, 19ñ8 percent of zinc intake, was not related to age, weight or RWG. ES of zinc varied from 0 to 22 percent of zinc intake. The other 2 recovered children were given a low protein formula, also at 'maintenance energy' intake. Of them, 4 non-oedematous children had RWG similar to the recovered children but NA of zinc (8ñ4 percent of intake) was lower than in the recovered children. TA (32ñ1 percent of intake) was lower than in the 2 recovered children on the same formula. The 3 oedematous children were sicker than the others; two were anorectic and therefore fed by nasogastric tube throughout their balances. TA were 5 and 9 percent in the tube fed and 21 percent in the other child. NA of zinc was -28, +2 and -14 percent. Thus 2 children had a high ES of zinc while the other child had a low ES Zn; he was the only one with profuse diarrhoea. The very low TA Zn and negative NA in two of the three children show that zinc homeostasis was markedly deranged and that zinc deficiency was probably present. This is consistent with our previous finding of low plasma zincs in oedematous malnourished children. The findings imply the need for zinc supplementation of severely malnourished children, in particular those with oedema. They also imply that factors affecting zinc absorption include the child's age and/or weight, and the dietary zinc and/or protein content. This study was supported by the Medical Research Council and the Wellcome Trust (AU)

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 kwashiokor (23 cases). In all 11 children died (fatality rate 20 percent), 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.1-1, SD 0.444, range 0.50-2.45) compared with the normal value at this age of about 2 mmol.1-1. 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 percent 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. We agree with previous authors that the low serum values are evidence of phosphate depletion and suggest that phosphate might be added to the electrolyte solutions used in the early stages of recovery. However, reports of adverse effects indicate that this should be done with great care (AU)

Glyoxalase I activity in erythrocytes from severely malnourished children

The enzyme glycoxalase I (glyox I) is involved in metabolic detoxification, and requires glutathione (GSH) as a cofactor. Given the low concentration of whole blood GSH in children with oedematous malnutrition, it is possible that the function of this pathway may be compromised in these children. Glyox I activity was therfore assayed in erythocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (ñSEM) for the marasmic group (marasmus: 105 ñ 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 ñ 4/u/gm Hb) were not significantly different from controls (cont: 104 ñ 2u/gm HB)>. In the group with marasmic-kwashiorkor (M-K: 88 ñ 4u/g Hb) Glyox I activity was significantly lower in controls (p < 0.005), as well as in children with marasmus (p < 0.005), and kwashiorkor (p < 0.05). Enzyme activity was lower than normal in 45 percent of the MK group. Seven children died subsequent to admission; in five cases Glyox I activities were exceedingly low. There was a weak positive correlation between Glyox I activity and whole blood levels of GSH (r=0.215). We conclude that Glyox I activity is relatively unaffected in malnutrition, except in those with M-K and especially those who do not survive the acutely malnourished state (AU)

Pathology of the lungs in childhood malnutrition in Jamaica: light and electron microscopy

The autopsy records of 115 children with severe protein-energy malnutrition were reviewed. Sections of the lung histology showed evidence of bacterial pneumonia in 49 percent of cases. An additional 18 percentshowed bronchitis, bronchiolitis or interstitial pneumonitis. Aspiration of gastric contents was evident in 10 percent of cases; 6 percent showed pulmonary oedema and congestion. In the remaining cases, no lung pathology was identified (17 percent). In 8 cases, rapid autopsy examination permitted fixation of lung tissue for electron microscopy. These included 4 cases of bronchopneumonia, one of which was associated with viral pneumonia. Another interstitial pneumonitis, probably of viral aetiology, was also studied. Both these virus-associated cases showed loss of type I pneumocytes and hyperplasia of type II pneumocytes. Another patient with herpes simplex hepatitis showed necrotic emboli in pulmonary capillaries with virions, as well as colonies of interstitial bacteria. One patient with acute pulmonary oedema displayed severe endothelial cell swelling on electron microscopy. In one case, there was no evidence of respiratory changes, apart from desquamation of type I pnuemocytes. Useful information can be obtained on the fine structure of the lung, using samples taken soon after death. (AU)

The human rumen

The cow is a ruminant, and cow's milk has evolved to promote bacterial growth in the upper small bowel; whereas human milk has evolved to discourage bacterial growth. Examinations of the constituents of the two milks shows that their differences can be accounted for in terms of this difference in function. Children who are fed a calf's diet tend to develop a rumen. This may lead to chronic diarrhoea and malnutrition and may be a factor in diarrhoea ascribed to cow's-milk-protein allergy and lactose intolerance (Summary)

The measurement of rates of protein turnover, synthesis, and breakdown in man and the effect of nutritional status and surgical injury

Current concepts of protein turnover, synthesis and breakdown in man are reviewed. Emphasis is placed on the distinction between protein breakdown, by which constituent amino acids are released, and amino acid catabolism, which leads to the formation of excretory products, mainly urea and carbon dioxide. Methods of measuring overall rates of turnover, synthesis, and breakdown of body protein in man by the continuous or intermittent administration of radioactive or stable isotopes of amino acids are reviewed. Data from the published literature and from ongoing studies reveal that the overall rate of protein synthesis declines with age. There is close agreement between results obtained with different isotopes in normal adults. Malnourished infants have significantly lower rate of protein turnover, synthesis and breakdown before than after recovery. These finding may represent another example of metabolic adaptation in the malnourished child. After surgical trauma in adults the rate of protein synthesis is significantly reduced and neither protein turnover nor breakdown shows a significant change from preoperative values. It is concluded from these studies that the negative nitrogen balance found after injury is accounted for by reduction in protein synthesis and that protein breakdown remains unchanged after orthopedic operations. The relevance of these findings to the changes in nitrogen metabolism seen in infection is discussed (AU)

Trace elements: potential importance in human nutrition with particular reference to zinc and vanadium

Knowledge of the metbolic importance of trace elements is expanding rapidly, and human populations are being identified who suffer from deficiencies of elements other than iron and iodine. The roles these highly reactive elements play are diverse. They range from incorporation into single specific molecules in single tissues to incorporation into many proteins in all tissues, incorporated into large molecules. Consideration of zinc and vanadium metabolism draws this contrast strikingly. It would be naive to think that these elements are not nutritionally important or that their metabolism merely represents a repetition of the iron story, but 50 years later (AU)

Malnutrition and diabetes mellitus: a case study

A ten-year-old girl was admitted with marasmic kwashiokor, mucocutaneous candidiasis. Necator americanus and Trichuris trichiura infestation, small bowel overgrowth and faecal impaction due to acquired megacolon. During early recovery, she had an acute overt hyperglycaemic episode without ketosis. This responded rapidly to intravenous fluids and soluble insulin. She then gained 1 kg per week for 8 weeks on a recovery formula. During this, her blood glucose level fluctuated between 1.3 and 25.5 mmol/l. Abdominal X-rays and ultrasonography demonstrated diffuse pancreatic calcification. After 3 months, she was changed to a mixed diet and, later, a single daily dose of lente insulin. She ceased weight gain and began height gain. Six months after admission, she was discharged to a very poor home environment. However, she continued to gain weight and height though her blood glucose level remained poorly controlled. Her mental age increased from 50 to 56 months, over 10 months. Her mother also had diabetes mellitus but without pancreatic calcification. It seems that her primary problem was malnutrition. The cause of pancreatic calcification which presumably led to her brittle diabetes mellitus remains unclear. Gut stasis with ensuing pancreatic duct infection may have been largely responsible. Her monotonous diet, in particular, its relatively high carbohydrate content and the inclusion of `coldbush' tea, may also have contributed. In view of her continuing insulin dependence and her poor home situation, the prognosis remains guarded (AU)

What is the weanling's dilemma? Dietary faecal bacterial ingestion of normal children in Jamaica

Childhood gastroenteritis and malnutrition have been associated with a high bacterial contamination of weaning foods and bottle feeds in particular. We have cultured the bottle feeds of 90 well-nourished and 11 undernourished children aged 6-23 months. Four-fifths of the feeds had more than 10,000 viable faecal organisms/ml and two-thirds had more than 10,000 viable faecal organisms/ml and two-thirds had more than 100,000. The level of contamination did not differ between milks and porridges or with different methods of sterilization. There was no relationship between the level of contamination and nutritional status of the children. Those who were being breast fed at the time of sampling had expereinced fewer episodes of gastroenteritis. The results indicate that well-nourished children can ingest large numbers of viable faecal organisms with relative impunity, particularly if they are breastfed. The factors which dictate a child's response to a load of faecal bacteria should be explored to explain why some children do not succumb. (Summary)

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 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. (AU)

Plasma zinc and the clinical features of malnutrition

Human protein-energy malnutrition and zinc deficiency have common clinical features. These were related to the plasma zinc concentrations in 42 severely malnourished children. A low plasma zinc concentration was strongly associated with nutritional edema but not with the degree of edema or the plasma albumin concentration. In the absence of edema, there were significant relationships between plasma zinc concentrations and stunting, skin ulceration, and wasting. Infection was not necessarily associated with a lower zinc concentration. From these data, it can be predicted that a malnourished child with edema, skin ulceration, stunting, or severe wasting, will have a low plasma zinc concentration. (AU)