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BRANCH CHAIN AMINO ACIDS



Table of Contents
image Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis image Overview of randomized clinical trials of oral branched-chain amino acid treatment in chronic hepatic encephalopathy image Leucine metabolism in rats with cirrhosis. image Nutrient-induced thermogenesis and protein-sparing effect by rapid infusion of a branched chain-enriched amino acid solution to cirrhotic patients. image Effect of branched chain amino acid infusions on body protein metabolism in cirrhosis of liver. image Severe recurrent hepatic encephalopathy that responded to oral branched chain amino acids image [Branched-chain amino acids in the treatment of latent porto-systemic encephalopathy. A placebo-controlled double-blind cross-over study] image A prospective, randomized, double-blind, controlled trial. image Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism. image Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. image Branched-chain amino acid-enriched elemental diet in patients with cirrhosis of the liver. A double blind crossover trial. image Effect of euglycemic insulin infusion on plasma levels of branched-chain amino acids in cirrhosis. image Effect of glucose and/or branched chain amino acid infusion on plasma amino acid imbalance in chronic liver failure. image A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man. image [Pathogenesis of hepatic encephalopathy (author's transl)] image Clearance rate of plasma branched-chain amino acids correlates significantly with blood ammonia level in patients with liver cirrhosis image Nutritional treatment of liver cirrhosis with branched chain amino acids image Branched-chain amino acids - A highly effective substrate of parenteral nutrition for critically ill children with Reye's syndrome image Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats image Branched chain amino acids in the treatment of latent portosystemic encephalopathy. A double-blind placebo-controlled crossover study image Effects of amino acid infusions on liver regeneration after partial hepatectomy in the rat image Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis
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Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis

Journal of Nutrition (USA), 1996, 126/5 (1412-1420)

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 dining 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-tyraminecellobiose 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 x 10-3 . h-1) compared with noncirrhotic controls (45.08 x 10-3 . h-1) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 x 10-3 . h-1, P < 0.05) but not with conventional amino acid mixture (22.49 x 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.



Overview of randomized clinical trials of oral branched-chain amino acid treatment in chronic hepatic encephalopathy

Journal of Parenteral and Enteral Nutrition (USA), 1996, 20/2 (159-164)

Background: The role of oral branched-chain amino acid supplements in the prevention and treatment of chronic hepatic encephalopathy is not yet established, and conflicting opinions are expressed in authoritative textbooks. We aimed to review and pool the published controlled studies by means of meta-analytical techniques. Methods: A computerized search of published papers identified nine studies, controlled against placebo, energy, alimentary proteins, or casein. Their quality score was calculated according to the protocol of Chalmers. The value of the portal-systemic encephalopathy index was chosen as main outcome, because of lack of more significant clinical outcomes. To cope with differences in trial design and data presentation, individual data were requested to authors. Results: After 18 months, we received the individual data of only two studies, thus precluding any meta-analysis. Two studies, accounting for over 60% of total enrolled patients, were in favor of branched-chain amino acids. Their quality score was much better than that of the remaining seven negative small studies, carrying a significant risk of type II error. Conclusions: Based on the results of the two largest, long-term studies, the use of oral branched- chain amino acids in the prevention and treatment of chronic encephalopathy may only be proposed for patients with advanced cirrhosis, intolerant to alimentary proteins. Large, multicenter, long-term studies, considering more important clinical outcomes, are needed to provide definite answers to an aged question.



Leucine metabolism in rats with cirrhosis.

J Hepatol (DENMARK) Feb 1996, 24 (2) p209-16

BACKGROUND/AIMS: This study aimed to investigate the pathogenesis of reduced plasma levels of branched-chain amino acids leucine, isoleucine and valine in cirrhosis. METHODS: Cirrhosis was induced by intragastric administration of 36 doses of carbon tetrachloride in olive oil over a period of 12 weeks. Rats treated with oil alone served as controls. The rates of leucine turnover, clearance, oxidation and incorporation into proteins were evaluated using [1-14C]leucine, [4,5-3H]leucine and alpha-keto[1-14C]isocaproate 3 days after the last intragastric treatment in vivo and in the isolated perfused liver. RESULTS: In animals with cirrhosis we observed a profound fall in plasma branched-chain amino acid levels and significant decreases in leucine turnover, oxidation and incorporation into tissue proteins. A more pronounced fall in leucine incorporation in proteins resulted in a significant increase in the oxidized leucine fraction in rats with cirrhosis as compared to controls. Leucine clearance was higher in the cirrhosis group. Concomitant to the fall of whole body leucine turnover, decreases of leucine incorporation into protein and of ketoisocaproic acid decarboxylation were observed in the isolated perfused liver of rats with cirrhosis. However, leucine oxidation was increased compared with control rats. CONCLUSIONS: Our results indicate that the predominant mechanism of the decrease in plasma leucine levels in rats with cirrhosis is an increase in the oxidized leucine fraction associated with a decrease in leucine turnover. An increase in leucine oxidation in the cirrhotic liver is one of the mechanisms involved.



Nutrient-induced thermogenesis and protein-sparing effect by rapid infusion of a branched chain-enriched amino acid solution to cirrhotic patients.

J Med (UNITED STATES) 1996, 27 (3-4) p176-82

An increase in the resting energy expenditure (REE) on indirect calorimetry was observed by rapid intravenous infusion of a branched chain-enriched amino acid solution into cirrhotic patients. The increases resulted in nutrient-induced thermogenesis (NIT). The percentage of energy expenditure (EE) derived from protein decreased significantly with the infusion of the amino acids. The present pilot study demonstrates that branched chain amino acids can be utilized as energy substrates and a protein-sparing effect occurs in patients with liver cirrhosis.



Effect of branched chain amino acid infusions on body protein metabolism in cirrhosis of liver.

Gut (1986 Nov) 27 Suppl 1:96-102

Thirty seven patients with established cirrhosis of the liver were subjected to measurement of body protein metabolism using L-(1-14C) labelled leucine as a tracer. The effects of disease severity and those of solutions containing 0%, 16%, 35%, 53%, and 100% branched chain amino acids were evaluated. Significant increases in protein synthesis were noted with solutions containing 35%, 53%, and 100% branched chain amino acids, but in patients receiving 100% branched chain amino acids without additional essential amino acid supplement the increase in synthesis was matched by a significant increase in protein breakdown. Protein balance was thus improved only in patients receiving 35% and 53% branched chain amino acids. It was concluded that the high increase in protein breakdown in patients receiving 100% branched chain amino acids was undesirable, and such a solution should not be recommended for clinical use. (Editors note: This article indicates that overdosing branched-chain amino acids can be dangerous. Please follow the protocol precisely!)



Severe recurrent hepatic encephalopathy that responded to oral branched chain amino acids

American Journal of Gastroenterology (USA), 1996, 91/6 (1266-1268)

Hepatic encephalopathy is a neuropsychiatric syndrome occurring in patients with acute or chronic liver disease. Its pathogenesis remains unclear; however, it appears to be multifactorial. There are several conventional treatments for this condition, such as lactulose, neomycin, and protein restriction. There is significant controversy regarding the role of branched chain amino acids in the treatment of chronic hepatic encephalopathy. We describe a patient who had hepatic encephalopathy secondary to Budd-Chairi syndrome and a mesoatrial shunt that failed vigorous conventional therapy. She required multiple hospitalizations for severe recurrent encephalopathy. The patient was considered for a colonic exclusion procedure for the management of intractable encephalopathy. However, branched amino acid therapy was instituted as a last measure before the contemplated surgery, and the patient's encephalopathy responded in dramatic fashion, and she remained free from encephalopathy during a prolonged follow-up.



[Branched-chain amino acids in the treatment of latent porto-systemic encephalopathy. A placebo-controlled double-blind cross-over study]

Z Ernahrungswiss. 1986 Mar. 25(1). P 9-28

In a doubleblind cross-over placebo-controlled trial the efficiency of oral treatment with branched chain amino acids was investigated in 22 inpatients with liver cirrhosis. In all patients evidence of latent (subclinical) portalsystemic encephalopathy was obtained by using an extensive psychometric test programme. Patients received a defined diet of 35 cal/kg/day containing 1 g of protein. In addition, branched chain amino acids or casein in a dosage of 0.25 g/kg/day was administered in a cross-over fashion, each for 1 week. Semiquantitative nitrogen balance increased during both treatments, with a tendency towards a larger increase during branched chain amino acid treatment. At the same time ammonia concentration tended to decrease during branched chain 1amino acid treatment. Taking into account the cross-over design, significant improvements attributable to branched chain amino acid treatment could be demonstrated in psychomotor functions (line tracing, tapping, steadiness, auditory reaction time), attention (digit table), and practical intelligence (digit symbol, number connection test).



A prospective, randomized, double-blind, controlled trial.

J Parenter Enteral Nutr. 1985 May-Jun. 9(3). P 288-95

Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.



Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

Acta Med Okayama. 1983 Aug. 37(4). P 381-4

Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.



Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study.

Hepatology. 1983 Jul-Aug. 3(4). P 475-80

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.



Branched-chain amino acid-enriched elemental diet in patients with cirrhosis of the liver. A double blind crossover trial.

Gastroenterol. 1983 Nov. 21(11). P 644-50

In 14 patients with cirrhosis of the liver and portal-systemic shunts the effect of a branched-chain amino acid-enriched elemental diet on portal systemic encephalopathy, routine laboratory parameters and plasma amino acids was investigated. In addition to the standard therapy including protein restriction (40 g/day) the patients received 44 g of an amino acid-protein mixture containing 30% of branched-chain amino acids and placebo over 3 months in a crossover regimen. Plasma valine and leucine increased significantly, whereas all other amino acids, including the ratio (formula: see text), remained unchanged. The electroencephalogram, number connection test, clinical state and laboratory parameters were not influenced by therapy with branched-chain amino acids. Thus, orally administered branched-chain amino acids probably have no influence on hepatic encephalopathy but are an adequate source of nitrogen in patients with cirrhosis of the liver.



Effect of euglycemic insulin infusion on plasma levels of branched-chain amino acids in cirrhosis.

Hepatology. 1983 Mar-Apr. 3(2). P 184-7

To test the hypothesis that hyperinsulinism is responsible for reduced branched-chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched-chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched-chain amino acids was markedly higher in controls who had similar steady-state insulin levels. Not only did the level of branched-chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady-state insulin--a measure of tissue sensitivity to insulin--were markedly reduced in cirrhotics and positively correlated with the decline in branched-chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched-chain amino acid metabolism were reduced. Low branched-chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.



Effect of glucose and/or branched chain amino acid infusion on plasma amino acid imbalance in chronic liver failure.

J Parenter Enteral Nutr. 1981 Sep-Oct. 5(5). P 414-9

The characteristic amino acid pattern observed in chronic liver failure with high aromatic and low branched chain amino acid levels is considered to be consequent to increased muscle protein catabolism. The main catabolic stimulus has been attributed to hyperglucagonemia and to a reduced insulin/glucagon molar ratio. Intravenous administration of a solution containing branched chain amino acids and glucose to patients with chronic liver cirrhosis rapidly normalizes the plasma amino acid pattern. This effect may result from either a change in the insulin/glucagon ratio, induced by glucose, or from the anticatabolic influence of branched chain amino acids on muscle protein turnover. To discriminate between these two possibilities, a crossover study was carried out to determine the effect of a 24-hour infusion of either glucose alone, or glucose plus branched chain amino acids, in seven patients with chronic liver failure. Blood glucose, insulin, glucagon, free fatty acids, and amino acid levels were determined. Branched chain amino acids were much more effective than glucose (p less than 0.01) in decreasing the levels of aromatic amino acids. Conversely, the insulin, glucagon, and free fatty acid levels with glucose alone were not altered with the addition of branched chain amino acids. These findings suggest an anticatabolic effect of branched chain amino acids on muscle protein turnover and suggest that factors other than insulin and glucagon may be responsible for the characteristic plasma amino acid pattern present in chronic liver failure.



A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man.

Clin Sci (Colch). 1981 Jan. 60(1). P 95-100

1. Intravenous infusions of L-valine (600 mumol/min), L-isoleucine (150 mumol/min), L-leucine (300 mumol/min) and a mixture of the three branched-chain amino acids (70% L-leucine, 20% L-valine, 10% L-isoleucine; 270 mumol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P less than 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.



[Pathogenesis of hepatic encephalopathy (author's transl)]

Leber Magen Darm. 1977 Aug. 7(4). P 241-54

This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible. Encephalopathic patients with cirrhosis of the liver consistently showed elevated levels of the aromatic amino acids, phenylalanine, tyrosine and free tryptophan as well as methionine in serum, whereas levels of the branched chain amino acids, valine, leucine and isoleucine, were depressed. Comatose patients with fulminant hepatitis had markedly elevated levels of all amino acids, the results being greatly different from those of cirrhotic patients. Molar ratios of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) decreased both in cirrhotics with and without encephalopathy and in cases with fulminant hepatitis. Infusion of a commercially available L-amino acid solution in a cirrhotic patient induced a strikingly abnormal aminogram documented in hepatic encephalopathy. Therefore, effects of branched chain amino acid infusion on the deranged amino acid pattern were primarily studied for the purpose of improvement in hepatic encephalopathy by normalization of serum amino acid patterns. Elevated levels of the aromatic amino acids and methionine could be apparently depressed in a cirrhotic patient by this type of infusion but not in a case of fulminant hepatitis probably because of the poor utilization of these amino acids in severely impaired liver.



Clearance rate of plasma branched-chain amino acids correlates significantly with blood ammonia level in patients with liver cirrhosis

International Hepatology Communications (Ireland), 1995, 3/2 (91-96)

Reduced plasma free branched-chain amino acid (BCAA; valine, isoleucine and leucine) levels appear often in patients with liver cirrhosis and relate closely to the pathogenesis of hepatic encephalopathy and protein malnutrition in cirrhotics. To elucidate possible mechanism(s) of the BCAA decrease, plasma amino acid clearance rates were estimated by analyzing disappearance curves of amino acids which were infused at a rate of 0.1g/kg per 5 min in ten patients and eight controls. The clearance rate of total amino acids (TAA) was significantly lower while that of BCAA was significantly higher in cirrhotics than in controls. The relative clearance rate of BCAA (% TAA clearance) correlated significantly with the blood ammonia level. Since BCAA is required for the detoxication of ammonia in skeletal muscles, enhanced clearance of plasma BCAA may indicate the increased muscular uptake of BCAA. In conclusion, plasma BCAA reduction in cirrhotics is due, at least in part, to the enhanced plasma BCAA clearance, and hyperammonemia seems to be responsible for this enhancement. Supplementation with BCAA in these patients is reasonable to rescue this pathophysiological state of relative BCAA deficiency.



Nutritional treatment of liver cirrhosis with branched chain amino acids

(BCAA) Nutritional support in organ failure: proceedings of the International Symposium, 1990

The previous cross-over controlled trial showed that plasma FR and nitrogen balance were significantly increased during a 4-week period of BCAA granule (G) supplement. During a 12-week trial, plasma albumin and transferrin levels were significantly elevated in a dose-dependent fashion (8-16 g/day). In addition, a significant difference of cumulative survival rate (longer than two years) is observed between cirrhotics with and without BCAA-G over 6 months (n = 20 each). Moreover, %BCAA clearance rate from plasma is found to be significantly enhanced in cirrhotics as well as in Eck's fistula dogs, indicating that the decrease of plasma BCAA is due mainly to augmented utilization in the peripheral tissues (the muscle etc.). These findings now support the contention that nutritional treatment with BCAA-G is of practical importance for clinical improvement of the protein nutrition as well as for better quality of life in patients with decompensated liver cirrhosis.



Branched-chain amino acids - A highly effective substrate of parenteral nutrition for critically ill children with Reye's syndrome

CLIN. NUTR. (USA), 1987, 6/2 (101-104)

The use of a pure mixture of branched-chain amino acids (BCAA's) in combination with Nutramin(Reg.trademark) C SPOFA and glucose in a group of six paediatric patients with Reye's syndrome resulted in a significant metabolic improvement. Throughout the critical stage of the disease, administration of BCAA's in a dose of 1.0 g/kg b.w. per day led to remission of metabolic acidosis and a positive potassium balance. A negative nitrogen balance persisted. The resulting changes in plasma amino acid levels indicated high BCAA's clearance rates. Introduction of BCAA's to the complex therapeutic approach apparently helps to control the Krebs cycle and promotes glucose oxidation. In our group of six patients, five children fully recovered. Inclusion of BCAA's into the arsenal of therapeutic tools applied in patients with the hepatocerebral syndrome is likely to largely improve the prognosis in this condition constituting a serious medical challenge in paediatric patients.



Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats

BIOCHEM. MED. METAB. BIOL. (USA), 1986, 35/3 (367-375)

BCAA aminotransferase and BCKA dehydrogenase activities are increased in the mitochondrial fractions from the brains of hepatic failure rats treated with two-thirds removal of CClsub 4- injured liver. Cerebral leucine decarboxylation was accelerated, and it well correlated with arterial blood ammonia levels. Elevation of brain ammonia content following an intraperitoneal injection of ammonium acetate to hepatic failure rats could be prevented by intravenous infusion of BCAA. Significantly increased brain glutamic acid, glutamine, and alanine contents were noted. These results suggested that accelerated brain BCAA catabolism in acute hepatic failure rats reduce the neurotoxicity of ammonia by promoting the synthesis of glutamic acid and glutamine from BCAA.



Branched chain amino acids in the treatment of latent portosystemic encephalopathy. A double-blind placebo-controlled crossover study

GASTROENTEROLOGY (USA), 1985, 88/4 (887-895)

Branched chain amino acids have been recommended for the treatment of portosystemic encephalopathy based on the false neurotransmitter hypothesis. This hypothesis implies that by correction of the deranged amino acid pattern in the blood of cirrhotics, false neurotransmission and then portosystemic encephalopathy is improved. We conducted a double-blind crossover placebo-controlled trial in 22 inpatients with liver cirrhosis and obtained evidence of latent (subclinical) portosystemic encephalopathy using an extensive psychometric test program. Patients received a defined diet of 35 cal/kg.day containing 1 g of protein. In addition, branched chain amino acids or casein in a dosage of 0.25 g/kg.day was administered in a crossover fashion, each for 1 wk. Semiquantitative nitrogen balance increased during both treatments, with a tendency of a larger increase during branched chain amino acid treatment. At the same time ammonia concentration tended to decrease during branched chain amino acid treatment. Taking into account the crossover design, significant improvements attributable to branched chain amino acid treatment could be demonstrated in psychomotor functions (line tracing, tapping, steadiness, auditory reaction time), attention (digit table), and practical intelligence (digit symbol, number connection test).



Effects of amino acid infusions on liver regeneration after partial hepatectomy in the rat

J. PARENTER. ENTER. NUTR. (USA), 1986, 10/1 (17-20)

Administration of solutions high in branched-chain amino acids (BCAA) has been advocated in patients with severe liver failure; however, the effect of this treatment on the process of liver regeneration is still unclear. In the present study using rats we investigated the influence on liver regeneration of infusing solutions differing in amino acid content. After 75% hepatectomy, rats were infused via jugular vein with one of the following solutions: Sol A) 10% dextrose, Sol B) 10% dextrose + 3% amino acids (22% BCAA), Sol C) 10% dextrose + 3% amino acids (35% BCAA). Liver regeneration was estimated by measuring the incorporation of sup 3H-thymidine into DNA at five different time points after the operation. Peak regeneration occurred earlier in rats infused with the BCAA-enriched solution compared to animals infused with the standard amino acid solution or with dextrose alone. The increased incorporation of sup 3H-thymidine into DNA at 24 hr in rats infused with the BCAA-enriched solution was associated with elevated plasma levels of BCAA and decreased concentrations of tyrosine, phenylalanine, and methionine in comparison with the other two treatment groups. These results suggest that liver regeneration in rats can be accelerated by administering a parenteral nutrition solution tailored to normalize the deranged pattern of plasma amino acids associated with compromised liver function.



Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis

Journal of Trauma - Injury, Infection and Critical Care (USA), 1997, 42/2 (183-190)

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

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