Urinary 3-methylhistidine Excretion Research Articles

Effect of five hours of mixed exercise on urinary nitrogen excretion in healthy moderate-to-well-trained young adults.

Carbohydrates and fats are the primary energy substrates during exercise, but proteins can also contribute. When proteins are degraded in the body, the amino groups are mainly converted to urea and excreted. Therefore, nitrogen excretion has been used as a marker of protein degradation, but a clear conclusion has yet to be reached on the effect of exercise on nitrogen excretion. Thus, we tested whether exercise increases nitrogen excretion. Fifteen young, healthy, moderate-to-well-trained participants (4 females, 11 males, VO2max 54.4 ± 1.7 mL·kg-1·min-1; mean ± SEM) participated in a randomized, balanced cross-over design investigation consisting of 1 day with 5 h of exercise (exercise day, EX) and 1 day with no exercise (control day, CON). The participants recorded their dietary intake the day before from 16:00 and throughout the intervention day. They then repeated these dietary intakes on the second trial day. A standardized lunch was provided on both days. In addition, participants were allowed to consume almost protein-free snacks in EX to ensure the same energy balance during both trial days. Urine was collected throughout the whole testing period, and urinary 3-methylhistidine (3-MH) excretion was measured to examine muscular catabolism. The sweat rate was calculated during the exercise period. The urinary nitrogen and 3-MH excretions did not differ significantly between EX and CON (p = 0.764 and p = 0.953). The sweat rate was 2.55 ± 0.25 L in EX and 0.14 ± 0.15 L in CON (p < 0.001), and by estimating sweat nitrogen excretion, total nitrogen excretion was shown to differ with exercise. Our results showed that 5 hours of mixed exercise did not significantly impact urinary nitrogen and 3-MH excretions in healthy moderate-to-well-trained young adults.

Body weight reduction by exercise increases the urinary 3-methylhistidine excretion level with relatively positive nitrogen, sodium, and potassium balances when compared to dietary restriction

BackgroundRegarding changes in muscle mass, differences due to types of exercise and/or nutritional interventions, and associations with nutrient balances are still unclear. MethodsTo estimate changes in muscle mass during a body weight loss program using either a diet or exercise regimen, we investigated levels of muscle mass-related indices, and body contents of nitrogen, sodium, and potassium as measured by the balance method. Six healthy young adult male volunteers participated in two 10-day crossover experiments (20 days total). The first 5 days comprised an adjustment period (energy intake, 2656 ± 367 kcal/day (mean ± standard deviation)). During the second 5-day period, the participants either reduced their energy intake to 1770 ± 244 kcal/day (diet regimen) or exercised on a bicycle ergometer to expend 886 ± 122 kcal/day (exercise regimen). ResultsThe nitrogen, sodium, and potassium balances were significantly more positive during the exercise regimen than during the diet regimen. The urinary excretion levels of creatinine, 3-methylhistidine (3-MH), aldosterone, and catecholamines, and the 3-MH/creatinine ratio were significantly increased only during the exercise regimen. ConclusionsThe exercise regimen suppresses the decrease in muscle mass-related indices during body weight loss compared to the diet regimen with a relatively positive state of whole-body protein, sodium, and potassium balances, accompanied by an increase in sympathetic/adrenal cortical functions.

Carbohydrate Ingestion during Prolonged Cycling Improves Next-Day Time Trial Performance and Alters Amino Acid Concentrations.

Exercise with low carbohydrate availability increases protein degradation, which may reduce subsequent performance considerably. The present study aimed to investigate the effect of carbohydrate ingestion during standardized exercise with and without exhaustion on protein degradation and next-day performance. Seven trained male cyclists (V̇O 2max 66.8 ± 1.9 mL·kg -1 ·min -1 ; mean ± SEM) cycled to exhaustion (~2.5 h) at a power output eliciting 68% of V̇O 2max (W 68% ). This was followed by repeating 1-min work/1-min recovery intervals at 90% of V̇O 2max (W 90% ) until exhaustion. During W 68% , cyclists consumed a placebo water drink (PLA) the first time and a carbohydrate drink (CHO), 1 g carbohydrate·kg -1 ·h -1 , the second time. The participants performed the same amount of work under the two conditions, separated by at least 1 wk. A standardized diet was provided to the participants so that the two conditions were isoenergetic. To test the impact of carbohydrates on recovery, participants completed a time trial (TT) the next day. Carbohydrate ingestion maintained carbohydrate availability during W 68% and W 90% : total carbohydrate oxidation was significantly higher in CHO ( P = 0.022), and plasma glucose concentration was maintained compared with PLA ( P = 0.025). Next-day performance during TT was better after CHO ingestion (CHO, 41:49 ± 1:38 min; PLA, 42:50 ± 1:46 min; P = 0.020; effect size d = 0.23, small), as was gross efficiency (CHO, 18.6% ± 0.3%; PLA, 17.9% ± 0.3%; P = 0.019). Urinary nitrogen excretion ( P = 0.897) and urinary 3-methylhistidine excretion ( P = 0.673) did not significantly differ during the study period. Finally, tyrosine and phenylalanine plasma concentrations increased in PLA but not in CHO ( P = 0.018). Carbohydrate ingestion during exhaustive exercise reduced deterioration in next-day performance through reduced metabolic stress and development of fatigue. In addition, some parameters point toward less protein degradation, which would preserve muscle function.

High Protein Diet Has Beneficial Effects in Murine Muscular Dystrophy

In normal muscle there is a delicate balance between muscle protein synthesis and protein degradation. It is believed that this balance is disturbed in muscular dystrophy (MD) by decreased muscle protein synthesis and/or increased muscle protein degradation, resulting in net catabolism. In an attempt to reduce or reverse this catabolism, a high protein diet (HPD, 50% protein) was fed to dystrophic mice (129/ReJ dy) for 4 wk. The effects on muscle biochemistry, muscle function and muscle morphology were compared with those in dystrophic mice fed a normal diet (NPD, 20% protein) and in nondystrophic mice (NORM) also fed the 20% protein diet. Compared with NORM mice, NPD mice demonstrated greater rates of muscle protein synthesis (P < 0.05) as measured by the incorporation of labeled phenylalanine into muscle, greater protein degradation (P < 0.01) as measured by urinary 3-methylhistidine excretion, and lower muscle protein concentration (P < 0.01). When dystrophic mice were fed HPD for 4 wk, protein degradation was lower (P < 0.01) and muscle protein concentration greater (P < 0.01) than in NPD mice. These biochemical improvements were accompanied by greater morphological uniformity of muscle fibers, higher volume density of muscle fibers per unit area of muscle (P < 0.01), and lower shape factor (P < 0.01). Functionally, HPD led to improved muscle endurance (P < 0.01) and increased hind-limb utilization (P 0.01). We conclude that in murine dystrophy, HPD decreases net muscle catabolism, principally by decreasing muscle protein degradation, resulting in improvement in muscle morphology, strength and function.

Meat intake and risk of mortality and graft failure in kidney transplant recipients

ABSTRACTBackgroundIt is unknown whether meat intake is beneficial for long-term patient and graft survival in kidney transplant recipients (KTR).ObjectivesWe first investigated the association of the previously described meat intake biomarkers 1-methylhistidine and 3-methylhistidine with intake of white and red meat as estimated from a validated food frequency questionnaire (FFQ). Second, we investigated the association of the meat intake biomarkers with long-term outcomes in KTR.MethodsWe measured 24-h urinary excretion of 1-methylhistidine and 3-methylhistidine by validated assays in a cohort of 678 clinically stable KTR. Cross-sectional associations were assessed by linear regression. We used Cox regression analyses to prospectively study associations of log2-transformed biomarkers with mortality and graft failure.ResultsUrinary 1-methylhistidine and 3-methylhistidine excretion values were median: 282; interquartile range (IQR): 132–598 µmol/24 h and median: 231; IQR: 175–306 µmol/24 h, respectively. Urinary 1-methylhistidine was associated with white meat intake [standardized β (st β): 0.20; 95% CI: 0.12, 0.28; P < 0.001], whereas urinary 3-methylhistidine was associated with red meat intake (st β: 0.30; 95% CI: 0.23, 0.38; P < 0.001). During median follow-up for 5.4 (IQR: 4.9–6.1) y, 145 (21%) died and 83 (12%) developed graft failure. Urinary 3-methylhistidine was inversely associated with mortality independently of potential confounders (HR per doubling: 0.55; 95% CI: 0.42, 0.72; P < 0.001). Both urinary 1-methylhistidine and urinary 3-methylhistidine were inversely associated with graft failure independent of potential confounders (HR per doubling: 0.84; 95% CI: 0.73, 0.96; P = 0.01; and 0.59; 95% CI: 0.41, 0.85; P = 0.004, respectively).ConclusionsHigh urinary 3-methylhistidine, reflecting higher red meat intake, is independently associated with lower risk of mortality. High urinary concentrations of both 1- and 3-methylhistidine, of which the former reflects higher white meat intake, are independently associated with lower risk of graft failure in KTR. Future intervention studies are warranted to study the effect of high meat intake on mortality and graft failure in KTR, using these biomarkers.

FURTHER STUDIES ON URINARY 3-METHYLHISTIDINE EXCRETION AS AN INDIRECT INDEX OF DIETARY AMINO ACID ADEQUACY IN RATS

As a further step in the determination of the sen­sitivity of urinary 3-methylhistidine (3-MeH) to essential amino acid adequacy in diet, 36 male albino rats of the Wistar strain were divided into six groups +of six rats per group. Each group with an initial .mean live weight of 106.52 ± 0.54g was fed in in­dividual metabolic cages on a basal diet sup­plemented with graded levels of DL-methionine. Total methionine in diet ranged between 0.25 and 1.05%. The study lasted 10 days. The response of urinary 3-methylhistidine excretion to the graded levels of methionine in diet was compared to responses obtained from growth performance characteristics, plasma urea concentration, liver nitrogen and creatinine excretion. With the excep­tion of feed intake, all other indices of dietary pro­tein adequcy and efficient amino acid utilization viz growth rate, protein efficiency ratio, serum urea concentration, and creatinine excretion were significantly (P 0.05) to P 0.01) influenced by dietary methionine level. Maximum growth rate, liver N and urinary 3-methylhistidine were observed. in rats given 0.45% total methionine in diet. Supplementing the basal diet to contain 0.45% total,' methonine significantly (P 0.01) decreased serum urea concentration. Urinary 3-methylhistidlne excre­tion was found by regression analysis to be positively correlated to body weight gain (r = 0.73), feed intake (r = 0.61), urinary creatinine excretion (r = 0.74) and liver N (0.72) but negatively correlated to dietary methionine level (r = —0.41). We suggested that urinary 3-MeH excretion be added to the list of available indicts for dietary amino acid adequacy.

Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients.

A growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP). This 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (≥14 days of intensive care unit resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses. Of 145 sepsis patients enrolled, 19 (13%) died during their hospitalization and 71 (49%) developed CCI. The CCI patients were significantly older (mean, 63 ± 15 vs. 58 ± 13 years, p = 0.006) and more likely to be discharged to long-term acute care facilities (32% vs. 3%, p < 0.0001), whereas those with RAP were more often discharged to home or a rehabilitation facility. Six-month mortality was significantly higher in CCI as compared with RAP cohort (37% vs. 2%; p < 0.01). Multivariate logistic regression modeling revealed delayed onset sepsis (>48 hours after admission; odds ratio [OR], 10.93; 95% confidence interval [CI], 4.15-28.82]), interfacility transfer (OR, 3.58; 95% CI, 1.43-8.96), vasopressor-dependent septic shock (OR, 3.75; 95% CI, 1.47-9.54), and Sequential Organ Failure Assessment score of 5 or greater at 72 hours (OR, 5.03; 95% CI, 2.00-12.62) as independent risk factors for the development of CCI. The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion). The development of CCI has become the predominant clinical trajectory in critically ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism. Prognostic, level II.

新生児及び乳児における術後蛋白代謝の研究 : 尿中 3-methylhistidine 排泄量を中心に

新生児及び乳児における術後蛋白代謝の研究 : 尿中 3-methylhistidine 排泄量を中心に

Molecular characterization of skeletal muscle atrophy in the R6/2 mouse model of Huntington's disease

Huntington's disease (HD), a neurodegenerative disorder caused by mutant huntingtin, is characterized by a catabolic phenotype. To determine the mechanisms underlying muscle wasting, we examined key signal transduction pathways governing muscle protein metabolism, apoptosis, and autophagy in R6/2 mice, a well-characterized transgenic model of HD. R6/2 mice exhibited increased adiposity, elevated energy expenditure, and decreased body weight and lean mass without altered food intake. Severe skeletal muscle wasting accounted for a majority of the weight loss. Protein synthesis was unexpectedly increased 19% in gastrocnemius muscle, which was associated with overactivation of basal and refeeding-stimulated mammalian target of rapamycin (mTOR) signaling, elevated Akt expression and Ser(473) phosphorylation, and decreased AMPK Thr(172) phosphorylation. Moreover, mRNA abundance of atrogenes muscle ring finger-1 and atrophy F-box, was markedly attenuated during fasting and refeeding, and the urinary excretion of 3-methylhistidine was decreased, arguing against a role for the ubiquitin proteasome-mediated proteolysis in the atrophy. In contrast, mRNA expression of several caspase genes and genes involved in the extrinsic or intrinsic apoptotic pathway, caspase-3/7, -8, and -9 activity, protein abundance of caspase-3 and -9, Fas, and Fadd, and cytochrome c release were elevated. Protein expressions of LC3B-I and -II, beclin-I, and atg5 and -7 in muscle were upregulated. Thus, mutant huntingtin in skeletal muscle results in increased protein synthesis and mTOR signaling, which is countered by activation of the apoptotic and autophagic pathways, contributing to an overall catabolic phenotype and the severe muscle wasting.

Molecular Characterization of Skeletal Muscle Atrophy in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD), a neurodegenerative disorder caused by mutant huntingtin, is characterized by a catabolic phenotype. To determine the mechanisms underlying muscle wasting, we examined key signal pathways governing protein metabolism and cellular turnover in R6/2 mice, a well characterized transgenic model of HD. R6/2 exhibited increased adiposity, elevated energy expenditure, decreased body weight and lean mass. Protein synthesis was unexpectedly increased 19% in gastrocnemius muscle, which was associated with overactivation of basal and refeeding-stimulated mTOR signaling, elevated AKT expression and Ser473 phosphorylation, and decreased AMPK Thr172 phosphorylation. Moreover, muscle mRNA expression of atrogenes, ring finger 1 and atrophy F-box was markedly attenuated during fasting and refeeding, and the urinary excretion of 3-methylhistidine was decreased, arguing against a role for the ubiquitin proteasome-mediated proteolysis in the atrophy. In contrast, mRNA expression of genes involved in the extrinsic apoptotic pathway, caspase-3/7, −8 and −9 activity, protein expression of caspase-3 and −9, Fas, and Fadd, and cytochrome C release were elevated. Protein expression of LC3B-I and -II, beclin-I, atg5 and atg7 in muscle was up-regulated. Thus, an increase in apoptosis and autophagy appear to contribute to an overall catabolic phenotype and the severe muscle wasting.

Increased fat-free body mass and no adverse effects on blood lipid concentrations 4 weeks after additional meat consumption in comparison with an exclusion of meat in the diet of young healthy women.

Aims. To investigate whether changes of meat consumption can affect body composition and laboratory parameters in healthy, normal weight, young women without the aim to reduce body weight. Research Design and Methods. Women volunteered to eat low-fat meat in addition to their habitual diet (M) or to exclude meat products from their diet (NOM). After 4 weeks M and NOM were crossed over between subjects. Changes in nutrient intake, morphometrics and plasma parameters were compared during M and NOM. Results. Daily protein intake (means ± SD) was 2.25 ± 0.35 (25.2% of energy) and 1.15 ± 0.26 g/kg (14.0% of energy) during M and NOM, respectively. Fat-free body mass (FFM) increased during M (0.7 ± 1.0 kg, P = .02) and decreased during NOM (−0.8 ± 0.8 kg, P = .003). Body fat mass was unchanged. Concentrations of total cholesterol (−7%), LDL-cholesterol (−8%), and glucose (−4%) deceased significantly after M. Fasting glutamine concentrations were decreased by M and increased by NOM. Conclusions. Additional meat intake can increase FFM without adverse effects on blood lipid concentrations. Long-term studies are required. Urinary excretion of 3-methylhistidine could represent a biomarker for meat protein consumption.

3-Methyl Histidine Excretion in Starvation.

Urinary excretion of 3-methyl histidine was found to be reduced in starvation. Data show that the rate of muscle catabolism is reduced to a greater extent than muscle mass. Reutilization of amino acids appears not to be greatly enhanced during starvation.

Glucose Infusion Suppresses Surgery-induced Muscle Protein Breakdown by Inhibiting Ubiquitin-proteasome Pathway in Rats

It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear. Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated. Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion. The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling.

Effects of Peripartum Propylene Glycol Supplementation on Nitrogen Metabolism, Body Composition, and Gene Expression for the Major Protein Degradation Pathways in Skeletal Muscle in Dairy Cows

Early-lactating dairy cows mobilize body protein to provide amino acids that are directed toward gluconeogenesis and milk protein synthesis. Propylene glycol (PG) is a precursor of ruminal propionate, and feeding PG has been reported to improve energy supply by increasing blood glucose. Our hypothesis was that feeding PG could spare body protein by providing an alternative source of carbon for gluconeogenesis. The major objectives of this study were 1) to delineate the effects of pre- and postpartum PG supplementation in transition dairy cows on whole-body nitrogen balance, urinary 3-methylhistidine (3-MH) excretion, body composition, and gene expression profiles for the major protein degradation pathways in skeletal muscle; and 2) to characterize the changes in body protein metabolism during the periparturient period. Sixteen pregnant cows (7 primiparous and 9 multiparous) were paired based on expected calving dates and then randomly assigned within each pair to either a basal diet (control) or basal diet plus 600 mL/d of PG. Diets were fed twice daily for ad libitum intake, and PG was fed in equal amounts as a top dress from d –7 to d 45. All measurements were conducted at 3 time intervals starting at d –14±5, d 15, and d 38 relative to calving. Propylene glycol had no effect on whole-body N balance, urinary 3-MH excretion, or body composition. However, N balance was lower at d 15 and 38, compared with d –14. Urinary excretion of 3-MH was lower at d –14 than at d 15 and 38. Supplemental PG had no effect on body weight (BW) and all components of empty BW. On average, cows fed both diets mobilized 19kg of body fat and 14kg of body protein between d –14 and d 38. Supplemental PG had no effect on mRNA abundance in skeletal muscle for m-calpain, and the 14-kDa ubiquitin-carrier protein E2 (14-kDa E2) and proteasome 26S subunit-ATPase components of the ubiquitin-mediated proteolytic pathway; however, PG supplementation downregulated mRNA expression for μ-calpain at d 15, and tended to downregulate mRNA expression for ubiquitin at d 15 and 38. Relative to calving, mRNA abundance for m- and μ-calpain, ubiquitin, and 14-kDa E2 were greater at d 15 compared with d –14 and d 38. In summary, these results indicate that transitional effects on whole-body metabolism and gene expression for the Ca2+-dependent and ubiquitin-mediated proteolytic pathways in skeletal muscle were more pronounced than those elicited by PG supplementation.

Skeletal and cardiac myopathy in HIV-1 transgenic rats

The mechanism by which human immunodeficiency virus (HIV)-1 infection in humans leads to the erosion of lean body mass is poorly defined. Therefore, the purpose of the present study was to determine whether transgenic (Tg) rats that constitutively overexpress HIV-1 viral proteins exhibit muscle wasting and to elucidate putative mechanisms. Over 7 mo, Tg rats gained less body weight than pair-fed controls exclusively as a result of a proportional reduction in lean, not fat, mass. Fast- and slow-twitch muscle atrophy in Tg rats did not result from a reduction in the in vivo-determined rate of protein synthesis. In contrast, urinary excretion of 3-methylhistidine, as well as the content of atrogin-1 and the 14-kDa actin fragment, was elevated in gastrocnemius of Tg rats, suggesting increased muscle proteolysis. Similarly, Tg rats had reduced cardiac mass, which was independent of a change in protein synthesis. This decreased cardiac mass was associated with a reduction in stroke volume, but cardiac output was maintained by a compensatory increase in heart rate. The HIV-induced muscle atrophy was associated with increased whole body energy expenditure, which was not due to an elevated body temperature or secondary bacterial infection. Furthermore, the atrophic response could not be attributed to the development of insulin resistance, decreased levels of circulating amino acids, or increased tissue cytokines. However, skeletal muscle and, to a lesser extent, circulating insulin-like growth factor I was reduced in Tg rats. Although hepatic injury was implicated by increased plasma levels of aspartate and alanine aminotransferases, hepatic protein synthesis was not different between control and Tg rats. Hence, HIV-1 Tg rats develop atrophy of cardiac and skeletal muscle, the latter of which results primarily from an increased protein degradation and may be related to the marked reduction in muscle insulin-like growth factor I.

Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis.

An amino acid mixture rich in branched-chain amino acids and poor in aromatic amino acids was infused in six cirrhotics with altered plasma amino acid profile and normal mental state. The effect on muscle protein catabolism, as measured by urinary excretion of 3-methylhistidine, was assessed during two consecutive 3-day period in which patients received the amino acid mixture alone or in a hypertonic dextrose solution. During a 3-day basal period, cirrhotics showed increased rates of 3-methylhistidine excretion as compared to six matched healthy subjects. Both treatments reduced urinary 3-methylhistidine to normal. During treatment, branched-chain amino acids failed to normalize, plasma aromatic amino acid concentrations and ammonia declined, and alanine increased. Branched-chain amino acids are mainly oxidized in skeletal muscle with production of alanine. Reduced muscle protein catabolism following amino acid infusion is consistent with the physiological role of branched-chain amino acids in suppressing protein breakdown and stimulating protein synthesis. Long-term therapy with branched-chain amino acid-enriched mixtures may prove useful in advanced cirrhotics with severe muscle wasting.

Effect of an enteral diet supplemented with a specific blend of amino acid on plasma and muscle protein synthesis in ICU patients

Polytrauma patients are characterized by a negative nitrogen balance and muscle wasting. Standard nutrition is relatively inefficient to improve muscle protein turnover. The aim of this study was to investigate the effect of enteral nutrition (EN) supplemented with specific amino acids on protein metabolism in polytrauma patients. In a double blind study, 12 polytrauma patients were randomized to receive EN supplemented with either a mixture of cysteine, threonine, serine and aspartate (AA patients) or alanine at isonitrogenous levels (Ala patients). An intravenous infusion of l-[1-(13)C]-leucine was performed in the fed state between day 9 and 12 post-injury (Df) in patients and in a group of healthy volunteers (n=8) (EN+Ala) to measure whole body leucine kinetics, plasma and muscle protein synthesis rates. Nitrogen balance, 3-methyl histidine excretion were measured from day 3 to Df. The contribution of total plasma proteins to whole body protein synthesis was greatly increased, from 11% in healthy volunteers to about 25% in polytrauma patients. AA supplementation had no effect on nitrogen balance, leucine kinetics or plasma protein synthesis in patients. In contrast, the urinary excretion of 3-methyl histidine tended to decrease along the study in the AA supplemented group compared to an increase in the Ala group. Muscle protein synthesis tended to be higher in the AA group than in the Ala group (46%, P=0.065). During injury, an increased supply of cysteine, threonine, serine and aspartate could be able to better cover the specific amino requirements, thus resulting in improved muscle protein synthesis without impairment of acute phase protein synthesis.

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

The metabolic and endocrine disturbances associated with obesity and type 2 diabetes may impair the normal metabolic response to injury. Our objective was to investigate amino acid metabolism in endotoxaemic type 2 diabetic obese rats. A metabolic study was performed over 4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates (fa/+) divided into three groups: ad libitum-fed groups which underwent no treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p. injection, and pair-fed groups to the respective LPS groups. We evaluated the effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen loss and muscular proteolysis were measured daily by determination of urinary 3-methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels were measured. The data showed that ad libitum-fed ZDF rats had lower plasma arginine and glutamine levels than ad libitum-fed control rats. Compared with control rats, the LPS-treated ZDF rats presented lower thymic involution, a lower 3-MH:creatinine ratio and higher cumulative nitrogen balance. Against our working hypothesis, ZDF rats did not show an impaired metabolic response, and even appeared to be less sensitive to the stress.

Assessment of the nutritional state of patients with an intestinal fistula.

The arm muscle area, derived fat-free mass, urinary excretion of 3-methylhistidine and creatinine were measured serially in a group of patients with an intestinal fistula receiving prolonged nutritional support. While the two anthropometric tests appeared reasonable indicators of changes in muscle mass in these patients, the marked intra-individual variability in excretion of 3-methylhistidine and creatinine created problems in interpretation. It is suggested that more use be made of serial anthropometry in district general hospitals as an alternative, simple, measure of nutritional status.

The effect of elective surgery on 3-methylhistidine excretion.

Elective surgical operation in normally nourished patients is associated with an increase of up to 40 per cent in the urinary excretion of 3-methylhistidine during the first three postoperative days. This increase was statistically significant (P less than 0.01) on the second and third postoperative days. This probably represents a minor degree of increased muscle proteolysis, principally due to the operative trauma. The possible effect of postoperative starvation requires further elucidation.