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Institute of Nutrition, Academy of Medical Science, Moscow. USSR
Study of the response of nitrogen metabolism and other functions of the organism to various levels of protein intake permits investigation of the adaptation process. Our design for such experiments involved 30 young, basically healthy males who weighed an average of 70.5 kg. These individuals were divided into five groups: four test groups of five men each, and one control group of ten men. All of the subjects received a standard diet containing one and the same set of nutrients during the experimental period of 45 days; the sole difference between the diets was a change in the content of the protein, casein, a portion of which was replaced by carbohydrates, in particular starch, while maintaining equal caloric value. In this case, the control diet contained 15.1 9 N/day; the first group received 9.4; the second, 6.8; the third 4.6 9 N/day. During the first 21 days, the diet of the fourth group was protein-free, whereas during the next 24 days. it contained 12 9 of nitrogen. The caloric value of the diets was 3,000 kcal/day, on the average. During the control and post-experimental periods, a diet of natural products was used which was close to the control diet in chemical composition and caloric value (table 1). It was established that under conditions of inadequate protein supply in the food in the course of 45 days. the overwhelming portion of the clinical and physiological changes in the functions of a number of organs turned out to be poorly delineated. During this period of observation, even among the subjects who were on a low-protein or protein-free diet, we did not detect significant changes in the cardiovascular system, the gastro-intestinal tract, neuromuscular system, the central nervous system, or the urinary function. There were no clear shifts in the lipid, carbohydrate, vitamin or basal metabolism, or in the activity of the enzymes studied, with the exception of a marked lowering (360 per cent) in the activity of trypsin among the subjects on the protein-free diet.
Of the clinical and physiological indices, only the changes in body weight called attention to their dependence upon the level of protein in the diet. The character of the changes in body weight from initial levels (the less protein consumed, the greater the loss of weight) attests to the pathogenic cause of the decreases noted.
TABLE 1. Composition of the Casein Diet
|Protein (g/day)||Fats (g/day)||Carbohydrates (g/day)||Calories in kcal/day|
a. Figures in brackets indicate the amount of total nitrogen in g/day
The results indicate that during early or mild forms of protein deficiency, disorders in the functioning of the majority of the organs and tissues of the organism are practically non-existent. Hence, the important conclusion that a differential diagnosis of such states with respect to the clinical and physiological data alone is extremely difficult, and the lack of obvious clinical symptoms does not exclude the presence of protein deficiency in the diet. On the other hand, the presence of frank clinical symptoms is a reflection of disorders related to protein deficiency.
In connection with the poor specificity of the methods of clinical diagnosis in marginal forms of protein deficiency, our greatest effort was directed towards an evaluation of the significance of biochemical indices, which turned out to be clearly expressed. Among these the most important are changes in the indicators of nitrogen metabolism (table 2). It was established that when there is a decrease in dietary protein from 15.1 to 9.4 and 4.6 g/day, or when there is a complete absence of protein, changes occur in the organism that can be distinguished as the beginning phase of protein deficiency.
By the seventh day of the experimental period there was a significant reduction in the excretion in the urine of overall nitrogen by factors of 2, 2.3, 3, and 5; of urea by 1.7, 2.4, 3.4, and 7.7 times, of ammonia by 1.8, 2.2, 2.4, and 3.2; of amine nitrogen by 1.2, 1.3,1.5, and 1.8; of uric acid by 1.1, 1.4,1.5, and 1.8; of creatinine by 1.2,1.4, 1.7, and 2.7; and, finally, of overall nitrogen in the faeces by 1.3, 1.4, 1.7, and 1.8, respectively (table 2). It should be noted that these reduced values were maintained to the end of the experimental period.
By the seventh to the tenth days of the post-experimental period, when the subjects of all the test groups were receiving the same amounts of protein as the control group, the excretion of all these components was restored to the level of the control values. Thus, the degree of reduction in the excretion from the body of nitrogenous substances was proportionate to the decrease in protein consumption. Under similar circumstances of protein deficiency in the diet, there occurred a shift in nitrogen metabolism to a more efficient level. This was also manifested in the restructuring of nitrogen balance, when considerably less food protein was required for its maintenance (fig. 1), and in the increase in its true assimilability. which reached almost 100 per cent during the state of least consumption (4.6 9 N/day) (table 2).
TABLE 2. Some Indices of Nitrogen Metabolism (Values Taken at the End of the Experimental Period) for Different Levels of Protein Intake
|Total nitrogen (g/day)||12.80 ± 0.90||7.40 ± 0 50a||5.50 ± 0 40a||4.40 ± 0 70a||2.50 ± 0.40a|
|Urea||20.30 ± 0.60||11.90 ± 0 50a||8.50 ± 0 60a||5.80 ± 0 40a||2.70 ± 0.30a|
|Ammonia||0.77 ± 0.02||0.42 ± 0.01a||0.36 ± 0.02a||0.32 ± 0.02a||0.24 ± 0.02a|
|Amino groups||0.28 ± 0.01||0.24 ± 0.01a||0.21 ± 0.01a||0.19 ± 0.01a||0.15 ± 0.01a|
|Uric acid||0.65 ± 0.02||0.59 ± 0.01a||0.48 ± 0.02a||0.43 ± 0.02a||0.36 ± 0.02a|
|Creatinine||1.95 ± 0.06||1.67 ± 0.07a||1.40 ± 0.06a||1.16 ± 0.07a||0.75 ± 0.05a|
|Total protein (g%)||8.50 ± 0.14||8.54 ± 0.09||8.63 ± 0.20||8.26 ± 0.22||8.20 ± 0.05|
|Albumin (g%)||5.56 ± 0.19||5.56 ± 0.14||5.82 ± 0.15||5.40 ± 0.40||5.18 ± 0.21|
|Globulin (g%)||2.94 ± 0.17||2.98 ± 0.15||2.81 ± 0.13||2.86 ± 0.37||3.02 ± 0.18|
|A/G coefficient||1.88 ± 0.16||1.89 ± 0.20||2.03 ± 0.11||2.00 ± 0.26||1.74 ± 0.17|
|V/A index||2.36 ± 0.39||2.27 ± 0.18||1.54 ± 0.16b||0.91 ± 0 13a||1.03 ± 0.36a|
|Total N (g/day)||1.33 ± 0.07||1.03 ± 0.08a||0.93 ± 0.05a||0.80 ± 0.04a||0.75 ± 0.03|
|N assimilability (%)||96.10 ± 0.66||97.80 ± 0.96||99.40 ± 0.87b||99.60 ± 0.66b||-|
|N balance (± g/day)||0.00 ± 0.40||0.00 ± 0.55||- 0.40 ± 0.20b||- 1.36 ± 0 32a||- 3.84 ± 0.36a|
a. P < 0.001
b. P < 0 05; otherwise P > 0.05
FIG. 1 Daily Urinary Excretion of Nitrogen.
William M. Rand
Massachusetts Institute of Technology
Leona R. Zacharias
Massachusetts Institute of Technology and Massachusetts General Hospital
For a population of healthy individuals, adolescence is the time when perhaps growth in height varies most. How quickly individuals grow during these years depends on just where they are in relation to physical maturity, in particular in relation to their own growth spurt. Thus, individuals of the same age may be growing at their fastest rate since early childhood, or they may have already reached their mature height and have a height-growth velocity of zero. The following data are part of a much larger study of the whole process of physical maturation, and are offered as a concrete illustration of the amount of variability in physical growth that can occur during these very important years.
These data were gathered from a population of girls who were nine or ten years old in 1965, living in Newton, Massachusetts, United States, a middle class community of about 100,000 just outside Boston. The sample of 338 girls is representative of those girls who were attending public schools in Newton. They were followed closely through menarche, and for approximately 20 menstrual periods thereafter, by means of questionnaires every four to six weeks. Independent, semi-annual measurements were obtained from the public schools covering the same period but extending it earlier to ages five or six. Measured and predicted heights of these girls are in good agreement with the current NCHS standards.
The Mathematical Model
The data for each girl were fitted to a Preece-Banes model of adolescent growth:
h(t) = P1 - P2/[exp (P3 (t - P4)) + exp (P5 (t - P4))]
From this model the various timings of the growth spurt can be determined for each girl, and the velocities at any time. Of particular interest here are the ages at which minimum pre-adolescent heightgrowth occurs (sometimes identified as the transition between childhood and adolescent growth) and the ages at which maximum post-childhood growth occurs (time of peak velocity).
Description of Adolescent Height Velocity
Table 1 shows the velocity percentiles for girls at various ages during adolescence. Table 2 shows these velocities for girls in various stages of their growth spurt.
TABLE 1. Height Growth Velocities at Specific Ages (n = 338)
|Age (years)||Mean (cm)||
Velocity (cm/yr) Percentiles
TABLE 2. Height Velocities at Specific "Growth" Events
|Event||Mean Age (years)||Mean Height (cm)||
Velocity (cm/yr) Percentiles
|V0 (minimum pre-adolesent velocity)||8.7||130.1||3.7||4.4||4.8||5.4||6.1|
|V2 (peak velocity)||11.6||147.7||5.8||6.7||7.5||8.7||11.0|
|Half year before peak velocity||5.7||6.4||7.2||8.1||9.2|
|One year before peak velocity||5.0||5.8||6.4||7.0||7.9|
Maria E. Río, Norma Piazza, H. Garcia, and Adriana Merlo
Department of Nutrition and Food Science, School of Pharmacy and Biochemistry. University of Buenos Aires, and Metabolic Unit, Haedo (Buenos Aires),, Argentina
The purpose of this study was to determine the optimal protein: energy (P:E) ratio for formulas used in supplementary feeding through the evaluation of the capacity of different diets to promote recovery in undernourished children.
Materials and Methods
From a sample of 443 children representative of those attending a supplementary feeding programme in Buenos Aires, 40 males were selected and warded in the Matabolic Unit from Monday to Saturday to be submitted to N balance and related studies (1, 2).
The children's ages ranged from 2 months 22 days to 21 months 4 days; they were all undernourished according to Gomez's classification, and the weight expressed on a height basis was between 66.9 and 92 per cent of the 50th percentile of the growth curves for Argentina (3).
Children were fed ad libitum by their own mothers, under the control of trained nurses, with commercial milk formulas: a modified milk supplying 4.7 cal/g dry weight with a P:E ratio of 0.11 (group 1), or a casein, lactose-free formula supplying 4.6 cal/g dry weight with a P:E ratio 0.17 (group 2). Diets were assigned at random. and a single diet was used throughout the balance study. At the beginning of the study, there were no significant differences between groups for average age. weight for age. weight for height, or height for age. Food intake was recorded daily and changes in weight were controlled over the three-day balance period.
Statistical analysis was performed by a variance test according to Scheffe at a significance level of P < 0.05 (4).
Ad Libitum Energy and Protein Intakes and Weight Gain
The average weight and the ad libitum energy and protein intakes of children, divided according to diet and age, are summarized in table 1. Results of intake are expressed by kg body weight and by day, and also as a ratio with respect to the FAD/WHO 1973 standard requirements for children of the same age (5). Weight gain is expressed as g/kg/d, and also with reference to the expected weight gain for normal children according to Cusminsky's standard (3).
This table strongly suggests that, whatever the age, the energy intake tends to be higher in group 1 than in group 2 and therefore also the ratio of energy intake to energy requirement was higher. Voluntary energy intake tends to decrease with age at the same time as weight increases. This observation was confirmed when total daily energy intake was expressed as a function of body mass (W0.73), and a close correlation was obtained independently of age (fig. 1). The regression equations were: Energy intake (day) = 241 W0.73 for group 1, and 206 W0.73 for group 2, the correlation coefficient being 0.55 and 0.7, respectively. Differences between slopes were significant (P < 0.01). The slope for group 2 was not significantly different from that obtained when the FAD/WHO standard requirements were expressed as a function of the 50th percentile of the Cusminsky chart for Argentina, (206 and 200, respectively).
The intake of group 1 remains significantly higher even when, in order to cancel differences in energy density of diets, results were expressed as net dry matter.
The results of plotting weight gain versus energy intake are shown in fig. 2. A clear influence of the P:E ratio on catch-up growth was observed when, because of the independence of the age factor shown in fig. 1, weight gain was grouped according to levels of energy intake as follows: below 110; between 110 130; 131 -150, and higher than 150 kcal/kg/d.
Children in group 2 gained more weight at any level of energy intake, although the difference was not significant beyond 150 kcal/kg/d. This agrees with protein intakes that were about 2.6 and 3.5 times greater than normal figures according to FAD/WHO for groups 1 and 2, respectively (table 1).
Interrelationships Between Catch-up Growth and Nitrogen Balance
In this study, weight gain was a linear function of nitrogen balance (WG = 0.037 x - 1.56, where x is nitrogen balance; r = 0.74, P < 0.05), the slope corresponding to an average content of 37 mg nitrogen per 9, i.e. 23 per cent in new tissue.
FIG. 1. Energy Intake as a Function of Actual Body Mass (W0.73), in Children Fed Ad Libitum.
FIG. 2. Weight Gain as a Function of Energy Intake.
TABLE 1. Energy and Protein Intakes and Weight Gain in Children Fed Ad Libitum
|Age (months)||Group||Average Weight (kg)||
|0-3||1||4 205||192.2||1.6||5 5||2.3||19.8||2.6|
|3-6||1||4 785||162 1||1.4||4.8||2.6||13.8||4.3|
|2||4.517||156.6||1 3||6.7||3 6||18.6||5.8|
|2||7 483||118.8||1.1||4.4||3.4||5.6||8 4|
FIG. 3. Weight Gain as a Function of Protein Intake and Weight Deficit
Interrelationships Between Catch-up Growth and Degree of Undernutrition
Under conditions of ad libitum feeding, weight gain can be analysed as a function of protein intake according to the model proposed by Morgan et al. for higher organisms (6). When our data were analysed, the general hypotheses of the model were confirmed, but the great scattering of dots suggested that some other factor was conditioning the response. The influence of the P:E ratio was discarded. because, when paired for protein intake, differences in weight gain were not significant.
Among the other possible factors involved, the degree of deficit was the most noticeable; therefore, the analysis was repeated, grouping weight gain data according to selected levels of weight for height, irrespective of diet (fig. 3). Visual inspection revealed that catch-up growth can be described by sigmoidal saturation curves, in which the asymptote, the maximal weight gain capacity, is about 1.5 times higher than the highest capacity for growth in extra-uterine life. This was seen in children with a 10 to 20 per cent deficit, and the asymptote was three times higher in those with a20 to 30 per cent deficit of weight for height. Data for children with a higher than 30 per cent deficit were too few to determine the asymptote value.
TABLE 2. Average Efficiency of Protein and Energy Utilization for Catch-up Growth, According to Children's Weight for Height (3)
|Weight for Height (%)||90-80||80-70||< 70|
|Percentage of population in the group||17.5||75.0||7.5|
|(Weight gain)/(Protein intake)(g/g)||2.0||3.1||4.9|
|(Energy Intake - 70 W0.73)/(weight gain)(Cal/g)||10.3||5.8||3.9|
The interaction between deficit and growth capacity was only observed when protein intake was over 3 g/k/d; below this level, as shown in fig. 3 for children fed 2 to 3 9 protein/kg/d, weight gain was dependent on protein intake but independent of the degree of depletion.
The greater capacity for gaining weight observed at the same level of protein intake as undernutrition increases seems to indicate increased efficiency. Data in table 2 confirms that, at least during the period of repletion until the normal range of weight-for-height is obtained, the greater the deficit, the greater the efficiency of protein and energy utilization to promote catch-up growth. No clear interaction between weight gain and deficit expressed as weight for age was found.
The results of this study do not support the concept that energy needs of undernourished children are far above normal during the period of recovery from malnutrition. On the contrary, children fed ad libitum with a diet providing the 0.17 P: E ratio were able to regulate energy intake according to the demands of their actual body mass, the observed increments with reference to the requirements of normal children being related only to small body size. On the other hand, the additional 20 per cent energy consumed by the group with the 0.11 P:E ratio suggests some adaptive mechanism tending to meet the level of protein necessary to reach maximal growth capacity determined by the weight deficit.
Since the capacity for increasing energy intake is limited by physiological mechanisms, the only possibility of reaching the unusually high levels of protein intake, adequate to support growth-rates several times higher than normal, is through modification of the P:E ratio. Moreover, an adequate ratio would prevent excess of energy intake that could result later in obesity.
On the basis of the results reported here, we suggest that during the acute stages of nutritional recovery, which can be considered as repletion of body tissue, undernourished infants need a percentage of protein calories similar to that required for other species that grow faster (7). It is our feeling that the adequate protein-toenergy ratio should approach normal figures as weight becomes normal for height; a long-term study to evaluate P:E-ratio influence on true catch-up, which includes linear growth, is now in progress.
1. F. Viteri and J Alvarado, "Evaluación de la Calidad de la Proteína en Humanos, con Enfasis en Metodología," in Recursos Proteínicos en América Latina (INCAP Publication L-1, 1971).
2. M E Rio, S.J. Closa, N.M. Parada. and M.L Portela "Evaluación Bioquímica del Estado Nutricional," Rev Asoc. Bio. Arg., 41:239 (1976).
3. M Cusminsky, Tablas de Crecimiento entre 0 y 4 Anos (Ministerio de Bienestar Social Subsecretaría de Salud Pública de la Provincia de Buenos Aires y Centro de Crecimiento V Desarrollo; Hospital de Ninos. La Plata)
4. H. Scheffe, The Analysis of Variance, chapter IV (Wiley, New York, 1959),
5. Energy and Protein Requirements. Report of a Joint FAO/WHO Ad Hoc Expert Committee (World Health Organization, Geneva, 1973 ) (WHO Technical Report Series, no. 522.)
6. P.H. Morgan, L. Preston Mercer, and N.W. Flodin. "General Model for Nutritional Responses of Higher Organisms,'' Proc. Nat. Acad Sci., 72:4327 (1975).
7. E.W. Bernhardt, ''Correlation between Growth Rate of the Suckling of Various Species and the Percentage of Total Calories from Protein in the Milk," Nature, 191 358 (1961)
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