Branched-chain Amino Acid Solution Research Articles

Effect of a single intravenous injection of branched chain amino acids on body temperature of cats undergoing general anesthesia

ObjectiveTo evaluate the effect of a single intravenous injection of branched chain amino acids (BCAAs) on body temperature in cats undergoing general anesthesia. Study designProspective, blinded, randomized, crossover, experimental study. AnimalsA total of 10 healthy adult cats (five female and five male). MethodsCats were anesthetized three times with three different treatments in a random order: 3 mL kg–1 lactated Ringer’s solution (LRS), 100 mg kg–1 BCAAs (B100) or 200 mg kg–1 BCAAs (B200) solution immediately before induction of anesthesia. After induction, rectal temperature was measured every 5 minutes. Blood samples were collected for the measurement of blood glucose (BG) just before induction, at the end of the 90 minute period of anesthesia, and 24 hours after anesthesia induction. The differences between baseline and each subsequent rectal temperature, and BG measurements were analyzed. Areas under the curve (AUCs) for temperature differences were calculated for each animal for the anesthetic period (AUCT0–90). Parametric or nonparametric data were analyzed by one-way repeated measures anova or Friedman test. A value of p < 0.05 was considered significant. ResultsThere were no significant differences in AUCT0–90 between groups: 41.6 ± 7.7 for LRS, 43.4 ± 6.9 for B100 and 42.9 ± 7.5 for B200 (p = 0.368). No significant differences were observed in BG between groups at 90 minutes and 24 hours after anesthesia induction (p = 0.283 and p = 0.089, respectively). The incidence of hypoglycemia [BG ≤ 3.17 mmol L–1 (57 mg dL–1)] after anesthesia tended to be higher in both B100 (4/10 cats) and B200 groups (3/10 cats) than in LRS group (1/10 cats). Conclusions and clinical relevanceA single, preanesthetic intravenous injection of BCAAs did not attenuate heat loss during anesthesia. More cats were hypoglycemic in the BCAA groups than in the LRS group.

The effect of an intravenous injection of branched chain amino acids on body temperature of cats undergoing general anesthesia

Introduction: Infusion of amino acids attenuates heat loss in anesthetized dogs but has not been studied in cats. This study evaluated a single injection of a compounded, 65 mg mL-1 branched chain amino acid solution (BCAAs) on body temperature in cats undergoing general anesthesia.

Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy.

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis. Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls. Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids

Background/Aims: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Methods: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Results: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. Conclusions: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent.

Intraoperative infusion of branched-chain amino acids in patients undergoing gastrointestinal tumor surgery.

BackgroundThe purpose of this study is to investigate the effects of intraoperative infusion of branched-chain amino acids (BCAA) in patients undergoing gastrointestinal tumor surgery.MethodsSixty-one patients with gastrointestinal tumors undergoing gastrointestinal surgery were enrolled and randomly assigned to receive an intraoperative infusion of 3-compound BCAA solution (N = 20), amino acids (AA) solution (N = 21), or normal saline (NS) (N = 20). Nasopharyngeal temperature, blood glucose (BG), plasma insulin, and blood free fatty acids (FFA) concentrations were measured at 30 min before and 10 min after induction (T0,T1), 30 min and 2 h after skin incision (T2,T3), and 1 h after tracheal extubation (T4). Intensity of shivering and pain was accessed at 1 h after extubation.ResultsThe temperature in the BCAA and AA group was significantly higher than that in the NS group at T4 (P = 0.014 and 0.033). The incidence of shivering in the BCAA and AA group was significantly lower than in the NS group (P = 0.027 and 0.012). BG increased in AA group at T3 and T4 (P = 0.001 and 0.045). The plasma insulin concentration increased in the BCAA and AA group from T1 to T3. The plasma FFA concentrations in the BCAA group were lower than in the AA and NS group from T2 to T4.ConclusionsIntraoperative BCAA and AA infusion alleviated postoperative hypothermia and shivering. BCAA infusion also inhibited fat mobilization, without adversely affecting blood glucose.Trial registrationChiCTR-TRC-14004668Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-015-0751-y) contains supplementary material, which is available to authorized users.

D-16 Thematic Poster - Exercise Training in Cardiac Patients

While branched-chain amino acids (BCAA) leucine is known to stimulate the activation of mTOR and protein synthesis, the contribution of leucine supplementation to the adaptive process and performance improvement to eccentric resistance training is unclear. PURPOSE: This study investigated the effect of BCAA on eccentric training efficiency in rats. METHODS: Male Wistar rats of 12 weeks of age were allocated into BCAA-supplemented (n=7), casein -supplemented (CS) (n=8) or non-supplemented (CONT) (n=8) groups. The BCAA group was fed a BCAA solution (1.35 g/kg, valine: leucine: isoleucine = 1:2:1) by oral gavage twice per day, and had free access to water containing BCAA (3% BCAA solution). The CS group was fed isonitrogen casein and CONT group received 1% hydroxypropyl methylcellulose solution (without nitrogen source) administered in the same manner as the BCAA group. Rats achieved one bout of eccentric contractions, elicited by forty intermittent electric stimulations in the tibialis anterior (TA) muscles every other day for 6 weeks. The isometric strength was monitored throughout the training period and assessed 24 hours after the last session in blinded manner. RESULTS: During the first 4 to 9 days of the training, the isometric strength of all groups declined by 57-62% of the initial value but increased consecutively thereafter. In the last two weeks of the training period, the isometric strength in the BCAA group exceeded that of CONT group by 8-10% (p<0.05) but the increase was not significantly different in the CS group compared to the CONT group (by 5-7%). The increase in the post training isometric force was statistically significant in the BCAA (34.0±2.8 mNm, p<0.05) as compared to the CONT group (25.3±1.9 mNm) but was not statistically significant in the CS group (29.1±1.4 mNm). The average cross-sectional area of the fibers with central nuclei was significantly larger in the BCAA (4291±117 μm2) and CS (4116±100 μm2) as compared to the CONT (3763±93 μm2) group. The muscle weight, myogenic regulatory factors, cytoskeletal protein and satellite cells increased significantly over time but there were no significant differences between the groups. CONCLUSION: These results suggest that BCAA supplementation may be an effective tool in facilitating adaptation to training and improve muscle strength.

Branched‐chain amino acids alter cbx1 and c‐fos gene expressions in brain cells (818.14)

Branched‐chain amino acids (BCAAs), including leucine, isoleucine and valine, have well‐studied effects as supplement including endurance performance improvement and life span extension. The potential adverse effects of BCAA supplement on brain such as neurotransmitter synthesis defect and in vitro neurotoxicity have been reported, but the molecular mechanism has remained unknown. The purpose of this study was to identify gene expression changes respond to BCAA supplementation in a brain cells. We conducted microarray experiments on total RNA samples isolated from brain cells supplemented with 0, 2, and 8mM of BCAA solution. Ontology analysis found that biological pathways such as chromatin organization and ncRNA processing and molecular functions such as transcriptional activity were altered via gene expression changes. In particular, down‐regulated expression of CBX1 and up‐regulated expression of c‐FOS are respectively likely to influence mammalian viability and have overall effects on brain cells through cell signaling. This study revealed that BCAA supplement results in the significant expression changes of genes showing epigenetic or transcriptional functions in the brain cells.Grant Funding Source: Supported by the NRF grant funded by the Korea government(MEST) (2012018819)

Comparison of the efficacy of parenteral glutamine and branched-chain amino acid solutions given as extra supplements in parallel to the enteral nutrition in head trauma

Summary Background & aims: We aimed to investigate the effects of parenteral glutamine and parenteral branched-chain amino acid solutions, given as extra supplements to standard enteral nutrition on nutritional parameters like prealbumin, transferrin levels, number of lymphocytes as well as systemic immune response syndrome (SIRS) and sepsis development, mortality and length of stay in ICU in severe head trauma patients.

Recovery of Brain Dopamine Metabolism by Branched-chain Amino Acids in Rats With Acute Hepatic Failure

A decrease in the serum ratio of branched-chain amino acids (BCAAs) to aromatic amino acids (Fischer ratio) reflects the severity of hepatic encephalopathy, and clinical improvement by dietary augmentation with BCAAs has been demonstrated. As behavioral alteration results from changes in central neurotransmission, we investigated the role of BCAA administration on changes in the levels of central neurotransmitters in acute liver injury. Male Wistar rats were subjected to liver ischemia by occluding the left portal vein and hepatic artery for 90 minutes. A 4% BCAA solution containing valine, leucine, and isoleucine was intraperitoneally administered 3 times (8 mL/kg, each) at 1 hour, 6 hours, and 24 hours after vascular reperfusion, and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were evaluated in the striatum by a microdialysis procedure. Although the extracellular concentration of dopamine was affected by neither liver ischemia nor BCAA injections, the level of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 34% in the ischemic group 24 hours after reperfusion. The 3,4-dihydroxyphenylacetic acid level was normalized by treatments with BCAAs. The improvement of deranged cerebral dopaminergic activity may be a contributing factor in the improvement of hepatic encephalopathy by BCAAs.

Inhibitory Effect of Aroma on the Bitterness of Branched-Chain Amino Acid Solutions

Nutritional products for patients with liver failure available on the Japanese market contain many branched-chain amino acids (BCAAs) such as L-leucine, L-isoleucine, and L-valine, which not only have a bitter taste but also strong, unpleasant odours, leading to low palatability. The palatability of these nutritional products can be significantly improved by the addition of flavoured powders containing various kinds of tastants (sucrose, citric acid, etc.) and odourants (fruit, coffee aromas, etc.). The specific effects of the aroma of flavoured powders have not yet been clearly evaluated. In the present article, the inhibitory effect of aroma on the bitterness of BCAA solutions was examined. The bitterness intensity of a BCAA solution at the same concentration as Aminoleban EN was defined as 3.5 (measured by a previously described gustatory sensation method). The bitterness threshold of a BCAA standard solution without added aroma was estimated to be 1.87, while those of BCAA solutions containing green-tea, coffee, apple, vanilla, or strawberry aromas were 2.02, 1.98, 2.35, 2.40 and 2.87, respectively, when evaluated by the probit method. This shows that the addition of an aroma can elevate the bitterness threshold in human volunteers. The green-tea and coffee aromas predominantly evoked bitterness, while the vanilla aroma predominantly evoked sweetness. Apple and strawberry aromas evoked both sweetness and sourness, with the apple aroma having stronger sourness and the strawberry aroma stronger sweetness. Thus, a 'sweet' aroma suppresses the bitterness of BCAA, with coexisting sourness also participating in the bitterness inhibition.

Effects of BCAA Supplementation on Plasma Amino Acids and on Subjective Fatigue and Muscle Soreness during Low-Intensity Prolonged Exercise

An increased concentration of plasma tryptophan (Trp) may increase serotoninergic activity in the brain, possibly leading to central fatigue during prolonged exercise. Supplementation branched-chain amino acids (BCAA) may prevent Trp uptake into the brain. However there are few reports concerning the effects of BCAA on physiological and psychological responses during low-intensity prolonged exercise. PURPOSE: The purpose of this study was to investigate the effects of BCAA supplementation on plasma amino acids, in particular the plasma free Trp concentration, and on subjective fatigue and muscle soreness during low-intensity prolonged exercise. METHODS: Eight healthy untrained male subjects who were 30 – 48 yrs with a body mass of 70.0 +/− 8.0 kg (mean +/− S.D.), height of 173.2 +/− 5.9 cm and a maximal oxygen uptake of 40.0 +/− 5.9 ml/kg/min performed 4 h (or until exhaustion) of cycling at 50 % VO max on two separate occasions, at least four weeks apart. During exercise, the subjects ingested either a 50-ml solution of BCAA (8 g/l) or flavored water (placebo) every 12 min. Blood samples were drawn before exercise, every 30 min during exercise, immediately post-exercise, and at 30 min and 4 hr during the recovery period. Samples were analyzed for plasma Trp and BCAA concentration. Subjective fatigue and muscle soreness were measured by the visual analog scale (10 cm) before exercise, after 2 h of exercise, immediately post-exercise, and 4 hr, 1 day and 2 day after the completion of exercise. HR and rectal temperature were recorded throughout the exercise. RESULTS: Exercise time was not different between the BCAA and the placebo trials. Plasma free Trp concentration decreased progressively during both trials. In the BCAA trial, plasma Trp concentration was significantly lower than the placebo trial at 90 min and 150 min (p <0.01). In the placebo trial, there was no change in plasma BCAA concentration, whereas plasma BCAA concentration was immediately increased in the BCAA trial (p <0.001). Therefore BCAA ingestion resulted in a significant reduction in the ratio of free Trp/BCAA during exercise. The rating of subjective fatigue significantly increased after 2 h of exercise, immediately post-exercise, and 4 hr after the completion of exercise in both trails. However, in the BCAA trial, the rating of subjective fatigue was lower than the placebo trial. CONCLUSION: The results of this study suggest that BCAA supplementation might suppress changes in the concentration of plasma free Trp and subjective fatigue during low-intensity prolonged exercise.

Branched‐chain amino acid (BCAA) supplementation decreases delayed‐onset muscle soreness (DOMS) induced by squat exercise in humans

We conducted a human study to examine the effects of BCAA supplementation on DOMS and muscle fatigue induced by exercise. 12 healthy female students (21-24 years old, BMI: 19.4 ± 0.5), who did not take regular exercise, participated in this study. The experiment was conducted with crossover and double blind design. The composition of the test solutions used in this study was as follows: a BCAA solution (200 ml) containing 5.5 g BCAA (I:L:V = 1:2.3:1.2), 1 g green tea powder, and 1.2 g non-nutritive sweetener; and a placebo solution (200 ml) containing the same ingredients as the BCAA solution, but substituting 5.5 g dextrin for the BCAA. In the morning on the exercise trial day, subjects ingested either test solution at 0.1 g BCAA or dextrin/kg BW 15 min before squat exercise. The squat exercise consisted of 7 sets of 20 squats/set with 3 min intervals between each set. During each set, squats were performed every 2 sec. The leg muscle power was measured 2 days after exercise (3rd day). DOMS evaluated by the visual analog scale (VAS) showed a peak on the 2nd and 3rd days in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo trial, reflecting to the maximal isometric strength of knee extension being higher in the BCAA trial. Muscle fatigue evaluated by the VAS tended to be lower in the BCAA trial than in the placebo trial during 5 test days. These results suggest that BCAA supplementation contribute to bring better conditions of muscle after exercise.

Improvement of regional cerebral blood flow after treatment with branched-chain amino acid solutions in patients with cirrhosis

Objective The administration of solutions rich in branched-chain amino acids leads to mental recovery from acute hepatic encephalopathy in patients with liver cirrhosis. However, the mechanism of action of branchedchain amino acids remains unclear. The purpose of this study was to evaluate the effect of intravenous infusion of branched-chain amino acids on brain perfusion in patients with liver cirrhosis. Methods Single photon emission computed tomography scans were performed in 14 patients with liver cirrhosis before and after the administration of branched-chain amino acids in a single-day split-dose protocol. The per cent change in regional brain perfusion was calculated in high frontal, parietal, temporal, occipital lobes and cerebellum. Thereafter, statistical parametric mapping was performed to identify brain regions with abnormal cerebral perfusion. Results Intravenous infusion of solutions enriched with branched-chain amino acids induced a 13-20% increase in regional cerebral blood flow. Cirrhotic patients had regions of significant hypoperfusion, as determined by statistical parametric mapping, in the left superior parietal and posterior cingulate as compared to the control group. This hypoperfusion of parietal and cingulate regions was not detected after treatment with solutions of branchedchain amino acids. Conclusions The results of the present study suggest that administration of solutions enriched with branched-chain amino acids improves cerebral perfusion in patients with cirrhosis.

Nutrition and liver diseases.

Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended.

The Effects of Branched Chain Amino Acid Infusion on Pain Perception and Plasma Concentrations of Monoamines

KIRVELÄ, O. A., J. JAATINEN, H. SCHEININ AND J. KANTO. The effects of branched chain amino acid infusion on pain perception and plasma concentrations of monoamines in healthy volunteers. PHARMACOL BIOCHEM BEHAV 60(1) 77–82, 1998.—Infusions of branched chain amino acids (BCAA) have been shown to have several CNS-mediated effects including antinociceptive action. We investigated the effects of BCAA infusion on pain perception, respiratory control, and plasma monoamine concentrations. Six healthy female volunteers were given in a double-blind, random, crossover design an 8-h infusion (1.75 ml/kg/h) of either (a) Ringers lactate, (b) conventional 4% amino acid solution, or (c) 4% BCAA solution with intervals of at least 48 h. Respiratory control was evaluated with continuous capnography. Pain perception was measured using dental dolorimetry for sharp pain, and pain transmitted by afferent C-fibers was evaluated with tourniquet test. Changes in vigilance were measured using critical flicker fusion technique. Evaluations were made for baseline, and after 2.5, 5, and 8 h. Plasma samples were collected at the same time points for amino acid and monoamine analysis. BCAA infusion resulted in significant increases of plasma concentrations of all BCAAs, with a simultaneous decrease in concentrations of aromatic amino acids. Of the measured monoamines and their metabolites dihydroxyphenylacetic acid (DOPAC) decreased, showing significant treatment effect for BCAA. Despite these changes no significant effect of BCAAs on respiratory control, vigilance, or pain perception was observed. In conclusion, despite significant changes in plasma concentrations of both amino acids and DOPAC, BCAA infusion did not show any clinically relevant antinociceptive effect.

Effects of Branched-Chain-Enriched Amino Acid Solution on Insulin and Glucagon Secretion and Blood Glucose Level in Liver Cirrhosis

Background: The aim of this study was to determine whether therapeutically used branched-chain amino acids (BCAAs) solution influences glucose metabolism in liver cirrhosis (LC). Methods: BCAAs solution (200 ml) was infused in LC patients at different stages, and plasma concentrations of glucose and pancreatic hormones were determined. Results

Influence of ingesting a solution of branched‐chain amino acids on perceived exertion during exercise

On two occasions, seven male endurance-trained cyclists performed exhaustive exercise on a cycle ergometer in the morning after they had performed a bout of exercise the preceding evening in an attempt to lower the muscle glycogen stores. The subjects exercised at a work rate corresponding to approximately 70% of their maximal oxygen uptake for 60 min, followed by another 20 min of maximal exercise. During exercise the subjects were given either a solution of branched-chain amino acids (BCAAs) or flavoured water (placebo). Every 10 min during exercise the subjects rated their perceived exertion and mental fatigue on two different Borg scales. During the 60 min exercise at a given work rate the subjects ratings of perceived exertion when they were given BCAAs were 7% lower, and their ratings of mental fatigue were 15% lower than when they were given placebo. In addition, the performance in the colour task of Stroops Colour Word Test performed after exercise was improved when BCAAs had been ingested during exercise, compared with the results from the placebo trial. There was no difference in the physical performance between the two trials measured as the amount of work done during the last 20 min of exercise when the subjects performed at their maximum. The plasma concentration ratio of free tryptophan/BCAAs, which increased by 45% during exercise and by 150% 5 min after exercise in the placebo trial, remained unchanged or even decreased when BCAAs were ingested.

Influence of ingesting a solution of branched-chain amino acids on plasma and muscle concentrations of amino acids during prolonged submaximal exercise

On two occasions, seven male endurance-trained cyclists performed sustained exhaustive exercise with reduced muscle glycogen stores. During exercise, the subjects were supplied in random order with an aqueous solution of branched-chain amino acids (BCAA) or flavored water (placebo). Ingestion of BCAA caused the concentration of these amino acids to increase by 135% in the plasma and by 57% in muscle tissue during exercise, whereas in the placebo trial there was no change or a slight decrease in the concentration in plasma and a decrease of 18% in the muscle. The plasma concentration of alanine increased by 48% during exercise when BCAA were ingested, and the increase in the muscle concentration of alanine during exercise was larger (70% versus 31% in the placebo trial), suggesting an increased rate of alanine production. Also, the plasma concentration of arginine increased by 14% during exercise when BCAA were ingested, whereas there was no change during exercise in the placebo trial. There was a smaller decrease in the muscle glutamate concentration during exercise in the BCAA trial (32% versus 47% in the placebo trial; p < 0.05), but, for the remaining amino acids, there was no difference between the BCAA and placebo trials. There was a significant decrease in the muscle glycogen concentration during exercise in the placebo trial, whereas only a small decrease was found in the BCAA trial (28 and 9 mmol/kg wet wt [ p < 0.05] in the placebo and BCAA trial, respectively). This might indicate that an increased supply of BCAA has a sparing effect on muscle glycogen degradation during exercise.

Oral Supplementation with Branched-Chain Amino Acids Improves Transthyretin Turnover in Rats with Carbon Tetrachloride-Induced Liver Cirrhosis

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight·d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight·d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 × 10-3·h-1) compared with noncirrhotic controls (45.08 × 10-3·h-1) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 × 10-3·h-1, P < 0.05) but not with conventional amino acid mixture (22.49 × 10-3·h-1). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.

Gastric emptying in humans: influence of different regimens of parenteral nutrition.

Controversy exists in the literature regarding the effect of parenteral nutrition on appetite. Earlier, several authors showed that healthy adult males receiving IV nutrition reduced their voluntary food intake by an amount that approximated 80% of the IV calories.1 This finding suggested a postabsorptive control of oral food intake. In view of this observation, the authors of this study sought to answer two questions: does parenteral nutrition decrease gastric emptying and does the administration of branched‐chain amino acids (BCAAs) alter the rate of gastric emptying?Nine healthy male volunteers between the ages of 20 and 31 years with a mean weight of 72 ± 10 kg were studied. Basal energy requirements were calculated using the Harris‐Benedict equation and were estimated to be approximately 1765 kcal/d. All subjects were maintained on a diet consisting solely of an oral liquid supplement composed of 40% carbohydrate, 20% protein, and 40% fat (Ensure, Ross Labs, Columbus, OH). Each subject served as his own control and was studied three times. The first 6 days of each study period were spent at home consuming the oral liquid supplement. On the sixth day, subjects were admitted to the hospital, and after an overnight fast, one of three parenteral solutions was infused over a 12‐hour period. The parenteral formulas consisted of Ringer's lactate, a standard parenteral solution, or a parenteral solution in which half of the amino acids used in the standard parenteral solution were replaced with BCAAs. The latter two formulas consisted of 40% carbohydrate, 20% protein, and 40% fat and supplied 85% of the subjects' estimated basal energy needs. After 6 hours of the parenteral infusion, subjects consumed 500 mL of technetium‐labeled Ensure within a 2‐minute period, and gastric emptying was then measured by scintigraphy. In addition, blood samples were drawn 5 hours after initiation of the IV infusion and 45 minutes after consumption of the oral supplement for analysis of plasma glucose, insulin, glucagon, triglyceride, and free fatty acid levels.The rate of gastric emptying within the first 10 minutes after ingestion of the oral supplement was most rapid when Ringer's lactate was infused (radioactivity lost from stomach was 1.63%/min). The rate slowly decreased over the subsequent 50 minutes until it reached a steady rate of 0.46%/ min. The initial rate of gastric emptying was significantly slower with the standard parenteral formula (0.67%/min) compared with the Ringer's lactate. However, the rate was not significantly different than that of the Ringer's lactate after 50 minutes (0.48%/min). The initial gastric emptying rate during infusion of the BCAA solution (0.83%/min) was between that of the Ringer's lactate and the standard parenteral solution. Fifty minutes after infusion of the BCAA solution, the rate decreased to 0.43%/min; this rate was slightly lower than that observed with the other two IV solution at this time point (Table I). Mean serum glucose levels never exceeded 122 mg/ dL, and there was no correlation between glucose concentrations and the rate of gastric emptying. There were no significant changes in free fatty acid or plasma glucagon concentrations.These results demonstrate that gastric emptying is delayed in normal healthy male subjects receiving 42.5% (~750 kcal) of their estimated basal energy requirements from parenteral nutrition over a 6‐hour period. In addition, the authors propose that the BCAA parenteral solution did not delay gastric emptying to the same degree as the other two parenteral solutions due to the ability of BCAAs to decrease serotonin synthesis in the brain. Serotonin is a neurotransmitter known to regulate food intake and inhibit gastric emptying. Thus the authors suggest that providing parenteral solutions enriched with BCAAs may improve voluntary food intake during and after parenteral nutrition administration. They conclude that the reduction in oral intake frequently seen in patients receiving parenteral nutrition may be a reflection of the parallel reduction in the rate of gastric emptying rather than a result of existing disease.