Improved Protein Balance Research Articles

Whole-body protein kinetics in critically ill patients during 50 or 100% energy provision by enteral nutrition: A randomized cross-over study.

Enteral nutrition (EN) is a ubiquitous intervention in ICU patients but there is uncertainty regarding the optimal dose, timing and importance for patient-centered outcomes during critical illness. Our research group has previously found an improved protein balance during normocaloric versus hypocaloric parenteral nutrition in neurosurgical ICU patients. We now wanted to investigate if this could be demonstrated in a general ICU population with established enteral feeding, including patients on renal replacement therapy. Patients with EN >80% of energy target as determined by indirect calorimetry were randomized to or 50% or 100% of current EN rate. After 24 hours, whole-body protein kinetics were determined by enteral and parenteral stable isotope tracer infusions. Treatment allocation was then switched, and tracer investigations repeated 24 hours later in a crossover design with patients serving as their own controls. Six patients completed the full protocol. During feeding with 100% EN all patients received >1.2 g/kg/day of protein. Mean whole-body protein balance increased from -6.07 to 2.93 µmol phenylalanine/kg/h during 100% EN as compared to 50% (p = 0.044). The oxidation rate of phenylalanine was unaltered (p = 0.78). It is possible to assess whole-body protein turnover using a stable isotope technique in critically ill patients during enteral feeding and renal replacement therapy. Our results also suggest a better whole-body protein balance during full dose as compared to half dose EN. As the sample size was smaller than anticipated, this finding should be confirmed in larger studies.

Branched-Chain Amino Acids and Branched-Chain Keto Acids in Hyperammonemic States: Metabolism and as Supplements.

In hyperammonemic states, such as liver cirrhosis, urea cycle disorders, and strenuous exercise, the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) is activated and BCAA concentrations decrease. In these conditions, BCAAs are recommended to improve mental functions, protein balance, and muscle performance. However, clinical trials have not demonstrated significant benefits of BCAA-containing supplements. It is hypothesized that, under hyperammonemic conditions, enhanced glutamine availability and decreased BCAA levels facilitate the amination of branched-chain keto acids (BCKAs; α-ketoisocaproate, α-keto-β-methylvalerate, and α-ketoisovalerate) to the corresponding BCAAs, and that BCKA supplementation may offer advantages over BCAAs. Studies examining the effects of ketoanalogues of amino acids have provided proof that subjects with hyperammonemia can effectively synthesize BCAAs from BCKAs. Unfortunately, the benefits of BCKA administration have not been clearly confirmed. The shortcoming of most reports is the use of mixtures intended for patients with renal insufficiency, which might be detrimental for patients with liver injury. It is concluded that (i) BCKA administration may decrease ammonia production, attenuate cataplerosis, correct amino acid imbalance, and improve protein balance and (ii) studies specifically investigating the effects of BCKA, without the interference of other ketoanalogues, are needed to complete the information essential for decisions regarding their suitability in hyperammonemic conditions.

Short-term amino acid infusion improves protein balance in critically ill patients.

IntroductionEvidence behind the recommendations for protein feeding during critical illness is weak. Mechanistic studies are needed to elucidate the effects of amino acid and/or protein supplementation on protein metabolism before larger clinical trials with higher levels of protein feeding are initiated.MethodsWe studied the effects of parenteral amino acid supplementation (equivalent to 1 g/kg/day) over the course of 3 hours on whole-body protein turnover in critically ill patients in the intensive care unit (ICU) during the first week after admission. Patients were studied at baseline during ongoing nutrition and during extra amino acid supplementation. If the patient was still in the ICU 2 to 4 days later, these measurements were repeated. Protein kinetics were measured using continuous stable isotope-labeled phenylalanine and tyrosine infusions.ResultsThirteen patients were studied on the first study occasion only, and seven were studied twice. Parenteral amino acid supplementation significantly improved protein balance on both occasions, from a median of −4 to +7 μmol phenylalanine/kg/hr (P =0.001) on the first study day and from a median of 0 to +12 μmol phenylalanine/kg/hr (P =0.018) on the second study day. The more positive protein balance was attributed to an increased protein synthesis rate, which reached statistical significance during the first measurement (from 58 to 65 μmol phenylalanine/kg/hr; n =13; P =0.007), but not during the second measurement (from 58 to 69 μmol phenylalanine/kg/hr; n =7; P =0.09). Amino acid oxidation rates, estimated by phenylalanine hydroxylation, did not increase during the 3-hour amino acid infusion. A positive correlation (r =0.80; P <0.0001) was observed between total amino acids and/or protein given to the patient and whole-body protein balance.ConclusionExtra parenteral amino acids infused over a 3-hour period improved whole-body protein balance and did not increase amino acid oxidation rates in critically ill patients during the early phase (first week) of critical illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0844-6) contains supplementary material, which is available to authorized users.

Fundamental determinants of protein requirements in the ICU

Currently, feeding the ICU patient is highly discussed. Energy feeding has been the topic of randomized studies, but protein feeding has not. Study results are contradictory on early feeding; however, little is known about early protein requirement. What is this protein requirement based on, therefore what are the fundamental determinants? Recent studies have addressed the importance of protein feeding and/or muscle (protein) wasting in critically ill patients. Targeted feeding has been shown to improve protein balance in one study, and infection rate in one study. Low muscle mass that is already present during ICU admission has been shown to be related to higher mortality, in two studies. Four studies have related muscle wasting to (protein) feeding strategies with very diverse results: Two small studies have reported no advantage [n = 15, computed tomography] or negative impact (n = 62, ultrasound, 50% sepsis patients) of protein on muscle wasting. Two studies, one small (n = 33, computed tomography) and one very large (n = 1372, Subjective Global Assessment), have reported a positive impact of (early) feeding on muscle wasting. Fundamental to adequate protein feeding in critically ill patients, at least 1.2 g protein/kg per day, is targeted energy feeding using indirect calorimetry. The level of protein requirement is related to fat free mass or muscle mass, which makes sex and BMI also relevant. Targeted early protein feeding is found to improve short-term outcome, reduction of muscle wasting and hospital mortality. Long-term outcome of protein feeding has not been studied. However, targeted protein feeding may be harmful in sepsis patients. Up to now, we lack biomarkers that provide caregivers with an instrument to increase protein feeding up to the individual protein requirement of the critically ill patient.

High-carbohydrate/low-protein–induced hyperinsulinemia does not improve protein balance in children after cardiac surgery

ObjectiveIn pediatric cardiac surgery, fluid-restricted low-protein (LoProt) diets account for cumulative protein deficits with increased morbidity. In this setting, we aimed to inhibit proteolysis by a high-carbohydrate (HiCarb)-intake–induced hyperinsulinemia and improve protein balance. MethodsThe effect of a HiCarb/LoProt (glucose 10 mg · kg−1 · min−1/protein 0.7 g · kg−1 · d−1) versus a normal-carbohydrate (NormCarb)/LoProt (glucose 7.5 mg · kg−1 · min−1/protein 0.3 g · kg−1 · d−1) enteral diet on whole-body protein breakdown and balance was compared in a prospective, randomized, single-blinded trial in 24 children after cardiac surgery. On the second postoperative day, plasma insulin and amino acid concentrations, protein breakdown (endogenous rate of appearance of valine), protein synthesis (non-oxidative disposal of valine), protein balance, and the rate of appearance of urea were measured by using an isotopic infusion of [1-13C]valine and [15N2]urea. ResultsThe HiCarb/LoProt diet led to a serum insulin concentration that was three times higher than the NormCarb/LoProt diet (596 pmol/L, 80–1833, and 198 pmol/L, 76–1292, respectively, P = 0.02), without differences in plasma glucose concentrations. There were no differences in plasma amino acid concentrations, non-oxidative disposal of valine, and endogenous rate of appearance of valine between the groups, with a negative valine balance in the two groups (−0.65 μmol · kg−1 · min−1, −1.91 to 0.01, and −0.58 μmol · kg−1 · min−1, −2.32 to −0.07, respectively, P = 0.71). The serum cortisol concentration in the HiCarb/LoProt group was lower compared with the NormCarb/LoProt group (204 nmol/L, 50–544, and 532 nmol/L, 108–930, respectively, P = 0.02). ConclusionIn children with fluid restriction after cardiac surgery, a HiCarb/LoProt diet compared with a NormCarb/LoProt diet stimulates insulin secretion but does not inhibit proteolysis further and therefore cannot be advocated for this purpose.

Current recommended parenteral protein intakes do not support protein synthesis in critically ill septic, insulin-resistant adolescents with tight glucose control

To investigate the effects of insulin infusion and increased parenteral amino acid intakes on whole body protein balance, glucose kinetics, and lipolysis in critically ill, insulin-resistant, septic adolescents. A single-center, randomized, crossover study. A medicosurgical intensive care unit in a tertiary university hospital. Nine critically ill, septic adolescents (age 15.0 ± 1.2 yrs, body mass index 20 ± 4 kg m(-2)) receiving total parenteral nutrition. Patients received total parenteral nutrition with standard (1.5 g · kg(-1) · day(-1)) and high (3.0 g · kg(-1) · day(-1)) amino acid intakes in a 2-day crossover setting, randomized to the order in which they received it. On both study days, we conducted a primed, constant, 7-hr stable isotope tracer infusion with [1-(13)C]leucine, [6,6-(2)H(2)]glucose, and [1,1,2,3,3-(2)H(5)]glycerol, in combination with a hyperinsulinemic euglycemic clamp during the last 3 hrs. Insulin decreased protein synthesis at standard amino acid and high amino acid intakes (p < .01), while protein breakdown decreased with insulin at standard amino acid intake (p < .05) but not with the high amino acid intake. High amino acid intake improved protein balance (p < .05), but insulin did not have an additive effect. There was significant insulin resistance with an M value of ~3 (mg · kg(-1) · min(-1))/(mU · mL(-1)) which was 30% of reported normal values. At high amino acid intake, endogenous glucose production was not suppressed by insulin and lipolysis rates increased. The current recommended parenteral amino acid intakes are insufficient to maintain protein balance in insulin-resistant patients during tight glucose control. During sepsis, insulin decreases protein synthesis and breakdown, and while high amino acid intake improves protein balance, its beneficial effects may be offset by enhanced endogenous glucose production and lipolysis, raising concerns that insulin resistance may have been exacerbated and that gluconeogenesis may have been favored by high amino acid intakes. Dose-response studies on the effect of the level of amino acid intakes (protein) on energy metabolism are needed.

Landscape Variation in the Diet and Productivity of Reindeer in Alaska Based on Stable Isotope Analyses

Productivity of a managed grazing system is dependent upon both the grazing strategy of ungulates and decisions made by humans. Herds of domestic reindeer (Rangifer tarandus tarandus) graze on discrete ranges of the Seward Peninsula, Alaska with variable production rates. We show that the 15N natural abundance of reindeer forages vary significantly and the δ15N value of collagen deposited in antler bone from spring until ossification was significantly correlated with the δ15N signature of the diet. Calf weight in June was related to isotopic signatures in antler and soft tissue of adult females, and was inversely correlated with the absolute differential between summer and winter serum δ15N values. This observation suggests that female reindeer with smaller calves had catabolized more body protein during winter than females in adjacent herds. Moreover, in herds with smaller calves, female reindeer consumed proportionately more shrubs in early spring resulting in a strong relationship between δ15N signatures of antler collagen deposited in May and calf weight. These data suggest female reindeer catabolizing relatively more body protein during winter may attempt to compensate by increasing consumption of high-protein catkins and leaf buds of shrubs during May. Herders with relatively smaller calves in their herds may be able to improve protein balance of reproductive females and thus increase calf productivity by increasing access to shrub habitats during spring.

Should Protein Be Included in CHO-Based Sports Supplements?

Should Protein Be Included in CHO-Based Sports Supplements?

Effects of glucagon-like peptide 1 on glycemia control and its metabolic consequence after severe thermal injury—studies in an animal model

Hyperglycemia with insulin resistance is commonly seen in severely burned patients and tight glycemia control with insulin may be beneficial in this condition. The most potent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), stimulates insulin secretion in a glucose-dependent manner. Because infusion of GLP-1 never reduces glucose levels to below ∼70 mg/dL, the risk of hypoglycemia by using insulin is reduced. In this study we investigated the metabolic effects of GLP-1 infusion after burn injury in an animal model. Male CD rats were divided in 3 groups: burn injury with saline, burn injury with GLP-1 treatment, and sham burn (SB). Burn injury was full thickness 40% total body surface area. The burn injury with GLP-1 treatment group received GLP-1 infusion via osmotic pump. Fasting blood glucose, plasma insulin, and plasma GLP-1 levels were measured during intraperitoneal glucose tolerance tests. Expressions of caspase 3 and bcl-2 were evaluated in pancreatic islets. In a subset of animals, protein metabolism and total energy expenditure were measured. Fasting GLP-1 was reduced in burn injury with saline compared to SB or burn injury with GLP-1 treatment. Burn injury with GLP-1 treatment showed reduced fasting blood glucose, improved intraperitoneal glucose tolerance test results, with increased plasma insulin and GLP-1 responses to glucose. GLP-1 reduced protein breakdown and total energy expenditure in burn injury with GLP-1 treatment versus burn injury with saline, with improved protein balance. Increased expression of caspase 3 and decreased expression of bcl-2 in islet cells by burn injury were ameliorated by GLP-1. Burn injury reduced plasma GLP-1 in association with insulin resistance. GLP-1 infusion improved glucose tolerance and showed anabolic effects on protein metabolism and reduced total energy expenditure after burn injury, possibly via insulinotropic and non insulinotropic mechanisms.

Regulation of protein metabolism by glutamine: implications for nutrition and health

Glutamine is the most abundant free alpha-amino acid in plasma and skeletal muscle. This nutrient plays an important role in regulating gene expression, protein turnover, anti-oxidative function, nutrient metabolism, immunity, and acid-base balance. Interestingly, intracellular and extracellular concentrations of glutamine exhibit marked reductions in response to infection, sepsis, severe burn, cancer, and other pathological factors. This raised an important question of whether glutamine may be a key mediator of muscle loss and negative nitrogen balance in critically ill and injured patients. Therefore, since the initial reports in late 1980s that glutamine could stimulate protein synthesis and inhibit proteolysis in rat skeletal muscle, there has been growing interest in the use of this functional amino acid to improve protein balance under various physiological and disease conditions. Although inconsistent results have appeared in the literature regarding a therapeutic role of glutamine in clinical medicine, a majority of studies indicate that supplementing appropriate doses of glutamine to enteral diets or parenteral solutions is beneficial for improving nitrogen balance in animals or humans with glutamine deficiency.

Effect of insulin on whole body protein metabolism in children with type 1 diabetes

Untreated type 1 diabetes (T1D) is associated with abnormalities in protein metabolism, leading to protein loss. These alterations can be particularly detrimental in children, affecting both normal growth and development. A better understanding of the effects of insulin on protein metabolism in children with T1D is essential for optimizing therapy and minimizing consequences of the disease.The aim of the present review is to outline the effects of insulin on whole body protein metabolism in T1D, focusing particularly on studies in children with T1D. Whole body protein degradation and amino acid oxidation are enhanced in children with T1D. Insulin reduces the rates at which body proteins are degraded. Whole body protein synthesis is either unaffected or reduced by insulin, even when insulin is administered together with amino acids to prevent insulin-dependent hypoaminoacidemia. Provision of insulin with oral nutrients improves protein balance by inhibiting whole body protein degradation, but does not affect protein synthesis. In children with T1D the anticatabolic effects of insulin on whole body protein metabolism are mainly exerted through a reduction in rates at which body proteins are degraded. Nutritional factors enhancing the anabolic effect of insulin need to be further elucidated.

Effect of urea or coconut cake supplementation on nutrient intake and digestion of Bali cows maintained on tropical grass hay.

Three rumen cannulated Bali cows were fed basal diet consisting of about 2 kg DM of medium quality grass hay (CP = 7.47%) together with ad libitum amount of low quality grass hay (CP = 3.5%) (HH). In the supplemented rations, this basal ration was supplemented with isonitrogenous amount of urea (HU) or coconut cake (HC). The experimental was on design 3 x 3 latin square aiming to study effects of different source of nitrogen supplementation on the intake of poor quality hay (PQH), total diet, nutrients supply and nitrogen utilisation by the animals. Changes in rumen environment and dry matter and protein degradation after supplementation were also investigated. Neither urea or coconut cake (CC) supplementation increased hay intake but the total dry matter intake was significantly higher (P < 0.05) in HC than in HH and HU. Digestibility of EE, CHO and GE but not NDF were also improved with CC supplementation. In contrast, CC supplementation tended to depress CF apparent digestibility. Rumen pH was significantly elevated (P < 0.05) with urea but it was reduced (P < 0.05) with CC supplementation. Both supplements increased rumen ammonia concentration, while total as well as individual VFAs remained unaffected. Dry matter and NDF rumen degradability tended to increase with urea but not with CC supplementation. Supplementation with coconut cake markedly improved protein balance while it was unimproved with urea supplementation. Key Words : Bali Cows, Urea, Coconut Cake, Digestion

Approach to Enteral Feeding in the PICU

The pediatric intensive care unit (PICU) environment poses unique challenges to achieving enteral nutrition (EN) goals for the critically ill child. Nutrition support in the PICU is often in conflict with the complexity of care provided to acutely ill children. A significant proportion of eligible patients do not receive optimal enteral nutrition for avoidable reasons. Early institution of EN is recommended and the gastric route is preferred because of ease of administration and reduced costs compared with the transpyloric route. In patients with poor gastric emptying or in cases where a trial of gastric feeding has failed, transpyloric or postpyloric feeding may be used to decrease the risk of aspiration and to improve enteral feed tolerance. However, there is no evidence of benefit for routine use of small bowel feeding in all patients admitted to the PICU. The placement of blind nasoenteric feeding tubes can be technically challenging, is not without complications, and requires local expertise and experience for successful placement and maintenance. A protocolized approach to selecting the optimal route and advancing enteral feedings may optimize EN delivery. Institutional practice guidelines based on consensus, available evidence, and national guidelines may decrease time to reaching caloric goal, improve protein balance, and potentially affect clinical outcomes. The rationale and challenges to the delivery and maintenance of optimal EN, and strategies to achieve optimal EN during critical illness, are discussed.

Insulin improves protein balance in adequately fed babies on extracorporeal life support

Insulin improves protein balance in adequately fed babies on extracorporeal life support

Regulation of proteolysis and optimal protein accretion in extremely premature newborns

Growth outcomes for extremely premature infants remain poor, and improving growth in this population will require a better understanding of how to limit proteolysis and promote protein accretion. Extremely premature infants exhibit high rates of proteolysis that are unrestrained by physiologic increases in insulin, intravenous amino acids, and full parenteral nutrition. Imbalances in current amino acid solutions may be in part responsible for the inability of parenteral nutrition to reduce proteolysis in preterm infants. However, amino acids in parenteral nutrition are effective for increasing protein synthesis in extremely preterm infants, which leads to improved protein balance. Current evidence suggests that early administration of 3 g amino acidskg−1d−1to extremely premature infants is safe and effective. Enteral nutrition may be more effective than parenteral nutrition in limiting proteolysis and producing protein accretion in preterm infants, but the protein content of current preterm formulas may be inadequate for supporting optimal growth in this population. Important areas of future research include determining whether altered intravenous amino acid solutions can better effect reductions in proteolysis, investigating the effect of enteral nutrition on proteolysis and protein accretion, and conducting a large randomized controlled trial of formula with a higher protein content.

Protein and energy metabolism response to the initial dose of infliximab in children with Crohnʼs disease

Tumor necrosis factor-alpha (TNF-alpha) may contribute to the alterations in protein and energy metabolism present in children with Crohn's disease (CD), who frequently suffer from growth disturbance. We hypothesized that anti-TNF-alpha therapy would reduce protein losses, due to decreased proteolysis and increased protein synthesis, and that anti-TNF-alpha therapy would decrease resting energy expenditure. Children with active CD underwent metabolic assessment immediately before and 2 weeks following initial infliximab infusion. Using the stable isotopes [d5] phenylalanine and [1-13C] leucine, 2 independent measures of protein metabolism were determined during fasting and in response to parenteral nutrition. Energy expenditure, determined by indirect calorimetry, was measured in fasting and parenterally fed states. Fifteen children completed the study. Following infliximab therapy, significant reductions in proteolysis (P < 0.05) were noted in the fasting state (8%-11%) and during parenteral nutrition infusion (10%-12%). Phenylalanine utilization for protein synthesis decreased significantly (8%-13%) following infliximab (P < 0.05). Protein balance was not significantly altered. No significant changes in energy expenditure were observed following infliximab in fasting or parenterally fed states. Supplementation with parenteral nutrition resulted in significantly decreased proteolysis (8%-21%; P < 0.05), increased protein synthesis (37%-45%; P < 0.01), and improved protein balance (P < 0.01) compared to the fasting state. Following the initial infliximab infusion in children with CD, proteolysis and protein synthesis were significantly reduced in the fasting and parenterally fed states. Supplementation with parenteral nutrition resulted in significant improvements in protein metabolism compared to the fasting state both before and after infliximab therapy.

Metabolic perioperative management: novel concepts

This review summarizes novel information regarding the role of metabolic control in the perioperative period. Managing perioperative metabolism has recently been shown to be an important way to improve outcomes in surgical care. In particular, postoperative insulin resistance and hyperglycemia have been linked to many common complications. Recent studies have explored the toxicity of hyperglycemia and suggest a causal relation between insulin resistance and complications in the postoperative state. Controlling glucose concentrations with insulin has been shown to also improve protein balance and fat metabolism. In addition, insulin may affect other hormones including insulinlike growth factor-I during surgical stress. Lastly, recent data suggest that hyperglycemia plays an important role in aggravating the inflammatory response, in that overflow of substrates in the mitochondria causes the formation of excess free oxygen radicals and may also alter gene expression to enhance cytokine production. Although overcoming insulin resistance by insulin infusion is one way of combating hyperglycemia, prevention of its development can also be achieved by using epidural blockade to reduce the release of adrenal stress hormones and to control pain, by preoperative carbohydrates instead of overnight fasting, and by minimal invasive surgical techniques. Minimizing the effects of insulin resistance has been shown to substantially improve outcome after surgical stress.

Short- and long-term effects of growth hormone (GH) replacement on protein metabolism in GH-deficient adults.

Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH replacement, but the protein metabolic changes are unclear. Using iv [(2)H(3)]leucine and oral l-[(13)C(1)]leucine infusions and dual emission x-ray absorptiometry, we compared leucine kinetics and body composition in eight GHD adults and eight healthy controls in the fasted and fed states, before and after 2 wk and 6 months of GH replacement. Leucine kinetics were not different between pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine oxidation decreased in the GHD subjects compared with baseline values [fasted, 41 +/- 6 vs. 30 +/- 5 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6 micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs. -3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131 +/- 6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/kg FFM.h (P < 0.05)]. After 6 months of GH treatment, these changes were not maintained in the fed state. The five GHD subjects with decreased FFM at baseline showed a significant increase after 6 months of GH treatment (P < 0.05). GH replacement in GHD acutely improves protein balance by stimulating synthesis and inhibiting catabolism. After 6 months, protein kinetics reached a new homeostasis to maintain the net gain in FFM.

The effect of glutamine on protein balance and amino acid flux across arm and leg tissues in healthy volunteers.

Glutamine is important in nitrogen transportation and the physiological control of acid-base regulation. In addition, it has been assumed that glutamine regulates protein balance in skeletal muscles based on findings in both experimental and clinical studies. However, little information on glutamine and its effect on protein dynamics in normal individuals is available. Therefore, the aim of this study was to evaluate whether glutamine improves protein balance and uptake of various indispensable amino acids across peripheral tissue in healthy individuals. Standard primed constant infusions of L-[ring-2H5]phenylalanine and [ring 3,3-2H2]tyrosine (2 micromol kg(-1) h(-1)) were performed after overnight fast in five healthy male volunteers before and during infusions of a standard and a glutamine/tyrosine enriched amino acid solution. Flux measurements of amino acids (AA) including 3-methylhistidine, glucose, lactate and free fatty acids (FFA) were performed across arm and leg tissues. Infusion of the standard AA solution (0.2 g N kg(-1) day(-1)) increased the net uptake of individual amino acids, but provision of the enriched solution (0.4 g N kg(-1) day(-1)) with increased amounts of glutamine and tyrosine seemed to compete unfavourably with the net uptake of other key amino acids as methionine and phenylalanine, which are indispensable in muscles for protein synthesis. Increased flux of amino acids across peripheral tissues did not influence on flux of glucose, free fatty acid and lactate. Glutamine provision did neither stimulate protein synthesis nor attenuate breakdown of either globular or myofibrillar proteins in skeletal muscles of healthy volunteers.

Effect of alanyl-glutamine on leucine and protein metabolism in endotoxemic rats.

Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) have a regulatory effect on protein metabolism and are the main donor for synthesis of alanine and glutamine in the skeletal muscle. This study was performed to investigate whether exogenous alanine or glutamine would affect leucine and protein metabolism in intact and endotoxemic rats. Rats were injected with endotoxin of Salmonella enteritidis or saline. Thirty minutes later, the effects of endotoxemia and L-alanyl-L-glutamine (AG) on leucine and protein metabolism were evaluated using a primed constant infusion of [1-14C]leucine, endotoxin, and AG (200 mg/mL) solution or an infusion of [1-14C]leucine without endotoxin or AG. The specificity of the effect of exogenous alanine and glutamine was evaluated by a single infusion of alanine, glutamine, and glycine in a separate study. Endotoxin treatment induced more negative net protein balance caused mainly by an increase in whole-body proteolysis. Protein synthesis increased in kidneys, colon, and spleen, while a decrease was observed in skeletal muscle. The impressive effects of AG were the decrease in plasma branched-chain amino acid (BCAA) levels, decrease in leucine oxidized fraction, and improvement of protein balance associated with a decrease in whole-body proteolysis. Similar changes in leucine and protein metabolism were induced by infusion of alanine or glutamine but not by infusion of glycine. IV administration of alanine or glutamine improves protein balance and decreases leucine oxidized fraction in postabsorptive state and in endotoxemia. Decreased proteolysis is the main cause of decreased plasma BCAA levels after AG treatment.