1. The adaptation of the diurnal cycle of nitrogen (N) homoeostasis during a change in protein intake was investigated with diurnal measurements of N and leucine balance and turnover during a reduction from a high to a moderate protein intake in normal adults. 2. In experiment 1, during a 9 day period after a reduction from 1.82 to 0.77 g of protein day −1 kg −1 , N excretion fell slowly at a similar rate in fed and fasted states so that the lowered intake was unable to replete any of the postabsorptive losses for 3 days. There was a marked negative N balance, which persisted throughout the study, although with a significant reduction in N losses in both fed and fasted states on day 4, balances during days 4–9 (−32.8 ± 28.3 mg of N day −1 kg −1 ) were less negative than during days 1–3 (−79.1 ± 60.4 mg of N day −1 kg −1 ). 3. In experiment 2, during a 14 day period after a reduction from 1.89 to 0.77 g of protein day −1 kg −1 , [1- 13 C]leucine oxidation and turnover were measured by primed intravenous infusion, during fasting and feeding in subjects before and on days 3, 7 and 14 after the dietary change. Leucine oxidation fell by 32% ( P < 0.05) on day 3 in the fed state and by 12% ( P < 0.05) during fasting, falling further in each case by day 7 with improved balance. N losses predicted from the leucine oxidation fell with the same time course as the measured N excretion in experiment 1, but the predicted losses were lower, so that the overall negative leucine balance on day 3 (−22 ± 17 mg of N day −1 kg −1 ) became positive by day 7 (+ 15 ± 21 mg of N day −1 kg −1 ). 4. Rates of protein synthesis and degradation calculated from leucine kinetics indicated that feeding the high protein diet resulted in a 60% inhibition of degradation and a 15% ( P < 0.05) stimulation of synthesis. With the moderate protein diet the improving fasting balance between days 3 and 7 was the result of a non-significant fall in degradation. Feeding the moderate protein diet abolished the stimulation of synthesis and significantly lowered the inhibition of degradation (31 ± 9%). The improving fed balance between days 3 and 7 was the result of changes in the rates of synthesis and degradation which were below the detection limits of the methods. The daily sum of fasted and fed rates of synthesis (4.33 g day −1 kg −1 ) did not change with the lowered intake, whereas the rate of degradation increased significantly from 3.61 to 4.26 g day −1 kg −1 ). 5. Thus, in response to a lower protein intake, adaptation of amino acid oxidation and N excretion occurs, with a similar pattern of gradual reductions in fed and fasted periods during the first week. Thus protein requirements are influenced by the habitual protein intake, which influences the nutritional demand for protein for repletion of fasting losses, the efficiency of such repletion and the consequent dietary need.

1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed increasing protein intakes. N balance was estimated during a 48 h period of consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of adaptation to diets containing 0.36 +0.01, 0.77 + 0.03, 1.59 +0.08 and 2.31 +0.65 g of protein day −1 kg −1 . N losses were determined from measured urinary N excretion corrected for changes in the body urea pool, and estimated faecal and miscellaneous losses. [ 13 C] Leucine and [ 2 H 5 ]phenylalanine balances were measured during a primed, continuous infusion of the two amino acids during the fasting and feeding phase on the second day. 2. Increasing fasting N losses were observed (47 +7, 60+6, 95+15 and 140+36 mg day −1 kg −1 ) on the four intakes, with corresponding increasing fed gains of 8.2+3.9, 40.2+7.1, 112+24 and 180+ 56 mg day −1 kg −1 . 3. Increasing fed-state amino acid gains with increasing protein intake were observed with both [ 13 C]leucine and [ 2 H 5 ]phenylalanine, whereas increasing fasting amino acid losses were confirmed with [ 13 C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly in the range of 10–50% lower than expected from the N excretion rates. This may reflect the timing of the amino acid balance measurements and non-uniform rates of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of both N and amino acid balances that the amplitude of the diurnal cycling of body protein N in human adults increases with increasing dietary protein intake. Thus one component of the protein requirement for N balance reflects a demand for repletion of fasting losses which increases with increasing habitual protein intake.

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 μg/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine ( P < 0.001) and production of ammonia ( P < 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4–40.6%), DNA content (by 24.2–34.7%), protein content (by 29.1–50.0%), villus height (by 16.3–26.4%) and crypt depth (by 20.3–29.6%) compared with other groups of septic rats. 6. The rate of intestinal [ 3 H]thymidine incorporation in vivo and thymidine kinase activity in vitro were significantly increased ( P < 0.001) in septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor. 7. The activity of jejunal glutamine synthetase was lower (by 66.3–90.0%) in septic rats treated with glutamine, epidermal growth factor or glutamine and epidermal growth factor, whereas glutaminase activity was increased (by 28.1–31.0%) in response to parenteral nutrition supplemented with glutamine only. 8. It is concluded that the administration of glutamine-supplemented parenteral nutrition, with or without epidermal growth factor, is beneficial to the small bowel of septic rats.

1. The effects of parenteral nutrition with or without xylitol and/or glutamine supplementation were studied in septic rats after 4 days of treatment. 2. Septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition survived sepsis significantly better than other parenteral nutrition-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5% compared with 54.5% in septic rats given parenteral nutrition without xylitol and glutamine, and 52.4% in septic rats treated with parenteral nutrition supplemented with glucose. 3. Xylitol- and/or glutamine-supplemented parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was positive in the rats given xylitol-supplemented parenteral nutrition and more positive when rats were treated with xylitol-glutamine-supplemented parenteral nutrition, as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased ( P < 0.001) in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 5. Hepatic protein and RNA contents were increased in septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein and RNA contents were markedly increased in muscles of septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. 6. The rates of incorporation of leucine/tyrosine into liver/muscle proteins in vitro were increased and the rate of muscular tyrosine release was decreased in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 7. It is concluded that the administration of xylitol- and/ or glutamine-supplemented parenteral nutrition is beneficial to septic rats and possibly to septic patients.

1. Urea kinetics were measured by using prime/intermittent oral doses of [ 15 N 15 N]urea in five healthy men taking formula diets adequate in energy and containing either 70 or 35 g of protein/day. In some studies the low-protein diet was supplemented with non-starch polysaccharides in the form of ispaghula husk or ripe bananas. 2. On the 70 g of protein/day diet urea production was 132% of intake. Only 54% of the urea produced was excreted in the urine with 46% being salvaged in the colon; 90% of the salvaged nitrogen was retained in the metabolic nitrogen pool. 3. On the 35 g of protein/day diet the small decrease in urea production rate compared with that on the 70 g of protein/day diet was not significant, but only 36% of the urea produced was excreted in urine, with the majority, 64%, being salvaged. 4. The extent of urea-nitrogen salvaging on the 35 g of protein/day diet was similar in magnitude to the decrease in nitrogen intake, with the effect that the sum of intake and salvaged nitrogen did not differ between the 35 and the 70 g of protein/day diets. This implies that quantitative control is exerted over the rate at which urea nitrogen is salvaged. 5. The addition of non-starch polysaccharides to the 35 g of protein/day diet had a demonstrable effect upon faecal weight and composition, but did not exert any significant influence upon urea kinetics. 6. It is concluded that large changes in the rate of urea production are not necessary for adaptation to a low-protein diet, rather the salvaging of urea nitrogen in the lower bowel appears to be an important mechanism through which the body adapts to a low-protein diet. The salvaging of urea nitrogen by the colon makes an important contribution to the conservation of body nitrogen.

1. The effect of total parenteral nutrition with or without glutamine enrichment was studied in septic rats after 4 days of treatment. 2. Septic rats treated with glutamine-enriched total parenteral nutrition survived sepsis significantly better than other TPN-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with glutamine-enriched total parenteral nutrition was 25% compared with 55% in septic rats given total parenteral nutrition without glutamine and 70% in septic rats given glucose. 3. Glutamine-enriched total parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was the least negative as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased ( P < 0.001) in response to glutamine-enriched total parenteral nutrition in septic rats. 5. The rate of protein synthesis was increased (21.2%) and the rate of protein degradation was decreased (35.5%) in response to glutamine-enriched total parenteral nutrition in septic rats. 6. It is concluded that the administration of glutamine-enriched total parenteral nutrition is beneficial to septic rats and possibly to septic patients.

1. The metabolic consequences of chronic ethanol feeding was investigated by assay of urinary metabolites. Male Wistar rats were fed a liquid diet containing 35% of total energy as ethanol or isovolumetric, isocaloric and isonitrogenous amounts of the same diet in which ethanol was substituted by isocaloric glucose (controls). 2. At 6 weeks the entire skeletal muscle mass was reduced by approximately 20%. The urinary excretion of nitrogen, urea and uric acid increased by between 23 and 128%. Urinary creatinine excretion was not significantly altered. 3. Urinary excretion of magnesium was significantly increased by 43%. Urinary excretion of sodium, potassium, calcium and phosphate was increased slightly (i.e. 5–22%), but this change was not statistically significant. 4. Proton n.m.r. spectroscopic analysis showed that ethanol feeding reduced the urinary excretion of citrate and 2-oxoglutarate (by approximately 50%), suggesting decreased citric acid cycle activity. There was an increased excretion of alanine (44%), but excretion of succinate and acetate was not significantly altered. Ethanol in the urine of ethanol-fed rats comprised approximately 2% of total ethanol intake and less than 1% of total energy intake. 5. Lactose was detectable in urine of ethanol-fed rats, but not in control rats, reflecting the reported decreased intestinal lactase activity and increased gut permeability in alcoholics. Urinary galactose excretion decreased by 41%, but relatively large increases in lactate excretion (50%) did not achieve statistical significance. 6. It was concluded that chronic ethanol feeding causes disturbances in whole-body nitrogen homoeostasis and alterations in intermediary metabolism.

1. Myofibrillar protein degradation has been measured by the rate of 3-methylhistidine excretion in premature infants weighing between 635 g and 1295 g. Analyses were made in conjunction with 1–3 day nitrogen balance studies. 2. In 56 balance studies in 36 infants, total muscle protein breakdown varied between 0·70 and 2·58 (mean 1·05) g day −1 kg −1 body weight while the percentage of total muscle protein degraded each day was between 3·3 and 8·3 (mean 4·8). 3. Both total and fractional rates of protein breakdown showed highly significant negative correlations with nitrogen retention but no relationship to total energy input. 4. Protein degradation was higher than average in infants who were losing weight at the time of the balance study, lower in infants who were gaining weight and higher in those who died within 2 weeks of the analysis. 5. Myofibrillar protein breakdown was not different between infants fed orally and those receiving total parenteral nutrition. 6. Generally the effects of nitrogen and energy status on muscle protein degradation in the premature infants are different from changes reported in adult human beings or adult rats. We suggest that this difference may be a consequence of the very limited energy reserves of the premature infant.

1. Rates of total protein turnover, synthesis and breakdown were measured in five children before and after recovery from severe protein-energy malnutrition and while receiving 0·6 g of protein and 397 kJ day −1 kg −1 . 2. These rates were calculated after giving doses of [ 15 N]glycine every 2 h along with the feeds and measuring the rate of excretion of [ 15 N]urea in urine. 3. Malnourished children had significantly lower rates of protein turnover, synthesis and breakdown than after they had recovered. 4. During recovery from protein-energy malnutrition, two children on a daily intake of 1·2 g of protein and 605 J/kg body weight, had rates of protein turnover, synthesis and breakdown that were twice as great as those found on admission and higher than after recovery. 5. On the study diet the malnourished children maintained their weight while the recovered children lost weight; the apparent nitrogen balance was more positive in the malnourished children. 6. In recovered children, the rate of protein synthesis was unchanged over a wide range of protein intake, whereas the rate of protein breakdown appeared to rise with a reduction in protein intake.

1. Aspects of nitrogen metabolism in the human neonate were assessed in one full-term infant and six premature infants by means of nitrogen-balance measurements, estimates of obligatory nitrogen losses and determinations of whole-body nitrogen turnover. 2. Our data indicate that the mean protein requirement for maintenance is 1·1 g of protein day −1 kg −1 and that 3·8 g of protein day −1 kg −1 should be sufficient for adequate growth in healthy premature babies. 3. The mean obligatory urinary, faecal and total nitrogen losses were estimated to be 24, 106 and 145 mg day −1 kg −1 respectively. These figures are compared with published values for older infants, and the possible metabolic basis for changes in nitrogen losses during growth and development is discussed. 4. Mean values for whole-body protein synthesis and breakdown were 26·3 ± 7·0 and 23·8 ± 7·4 g of protein day −1 kg −1 respectively. Dietary nitrogen intake accounted for 6–18% of the nitrogen flux through the metabolic pool; urea excretion accounted for 2% of the nitrogen flux. 5. The net protein gain, estimated from nitrogen-balance data, accounted for 9·6% of total daily protein synthesis. 6. These results are discussed in relation to published estimates of whole-body protein synthesis and breakdown at various ages. Their possible significance in the assessment of a ‘maintenance’ requirement for protein and amino acids during the period of rapid growth and development is also considered.

1. Nitrogen balance in uraemic patients on similar nitrogen intakes improves with increasing caloric intake in the range of 36–55 cal/kg body weight. 2. The degree of improvement in nitrogen balance is compatible with increased utilization of endogenous nitrogen probably as a result of increased dietary calories.