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Branched-chain amino acid interactions in skeletal muscle: isoleucine and L-alloisoleucine.

Parenteral administration of a mixture of branched-chain amino acid (BCAA) solutions is known to alter plasma levels of the BCAA (ILE, LEU, VAL), their corresponding alpha-ketoacids (KMV, KIC, KIV) and L-alloisoleucine (ALLO), a stereoisomer of ILE. Although variously formulated mixtures of BCAA are administered, the metabolic implications of individual BCAA interactions have been only partially elucidated. Using the incubated, isolated, and intact rat epitrochlearis muscle, we measured the effect of graded increases (0.05, 0.10, 0.5, and 1.0 mM) in media concentrations of a single BCAA or ALLO on (1) the rate of decarboxylation of the other BCAA, and (2) the release of branched chain ketoacids from muscle. A graded increase of media ILE concentration to 1.0 mM changed the decarboxylation of LEU by -28%, and the release of KIC by +23%, but VAL decarboxylation increased by +25%, and the release of KIV declined by -56%. A graded increase of media LEU to 1.0 mM increased ILE decarboxylation by +146%, and its corresponding ketoacid (KMV) by +61%. However, VAL decarboxylation changed by only +25% and KIV release declined by -65%. A graded increase in media VAL to 1.0 mM accelerated ILE decarboxylation by +37%, but KMV release was unchanged. Similarly, LEU decarboxylation fell by -26%, and the release of KIC by only +6%. ALLO 0.025 mM increased ILE release by +55% but had an inconsistent effect on ILE decarboxylation and did not alter protein synthesis or degradation (estimated by phenylalanine incorporation and tyrosine release, respectively). Increasing ILE did not affect ALLO release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Postoperative parenteral nutrition with high supply of branched-chain amino acids: effects on nitrogen balance and liver protein synthesis.

Branched-chain amino acids (BCAA) stimulate muscle and liver protein synthesis in vitro. The significance of this action in catabolic conditions in vivo remains controversial. The effects of a high supply of BCAA in total parenteral nutrition (TPN) on nitrogen balance and liver protein synthesis were studied in a postoperative rat model. After standard operative trauma TPN was commenced with one of two isocaloric programs (I: 20.1% BCAA and II: 50% BCAA) and continued for 48 hr. The relative rate of liver protein synthesis, measured after TPN in vitro by perfusion with 14C-leucine, was similar in both groups (I: 53.4 +/- 17.3 and II: 49.0 +/- 27.3 arbitrary units of synthesis rate, mean +/- SD). The cumulative nitrogen balance was positive with both regimens and was not improved by the high supply of BCAA (I: 2.02 +/- 0.81 and II: 1.87 +/- 0.63 gN/kg/48 hr mean +/- SD). We conclude that after moderate surgical trauma TPN with a high supply of BCAA offers no advantage over conventional TPN.

Albumins↗

Prospective study on the efficacy of branched-chain amino acids in septic patients.

The metabolic response to sepsis is characterized by increased proteolysis and gluconeogenesis, reduced protein synthesis, and negative nitrogen balance. The effects of a solution with a high proportion of branched-chain amino acids (BCAA) on the nutritional state of septic patients were evaluated. Eighty patients with peritonitis were divided into two groups of 40 patients; group 1 was administered a solution with 22.5% BCAA and group 2 with 45% BCAA. The following parameters were evaluated: anthropometrics, creatinine/height index, urinary 3-methylhistidine, nitrogen balance, stress index, albumin, prealbumin, transferrin, retinol binding protein, lymphocytes, delayed cutaneous sensitivity tests, studies of hepatic function, and plasma aminogram. In group 2 a more positive nitrogen balance, a greater drop in the stress index, a rise in plasma prealbumin and retinol binding protein levels, an increase in the creatinine/height index, and a more marked fall in the urinary excretion of 3-methylhistidine were found. When solutions with a high BCAA content were administered, there was an increase in the plasma concentrations of these amino acids in the BCAA/aromatic amino acid quotient and a decrease in the aromatic amino acids. Plasma concentrations of leucine and valine achieved very high, potentially toxic, levels at 15 days when solutions with high BCAA content were used. It is concluded that solutions with BCAA are advisable for use in the septic patient in the increased protein catabolic phase, where positive nitrogen balance, a reduction in muscle protein catabolism, and faster recovery of muscle and visceral protein were obtained.

Aged↗

Optimal ratio of individual branched-chain amino acids in total parenteral nutrition of injured rats.

In this study, we investigated the optimal ratio of individual branched-chain amino acids (BCAA) in a balanced amino acid infusion in laparotomized rats. The total BCAA contents of four amino acid infusions were fixed at 31% of total amino acids. The weight ratios of individual BCAA (isoleucine:leucine:valine) in the solutions were 1:0.5:1, 1:1:1, 1:2:1, and 1:4:1, respectively. The laparotomized rats were infused with about 140 mg (experiment 1) and 100 mg (experiment 2) of nitrogen and 10 g of glucose daily for 7 days. In both experiments, no marked difference was observed in the mean cumulative 7-day nitrogen balance and the urinary 3-methyl-histidine levels of all the groups. The BCAA concentrations and the molar ratios of individual BCAA in plasma were disarranged by the infusion of the 1:0.5:1 and 1:4:1 solutions. The infusion of the 1:1:1 and 1:2:1 solutions tended, however, to allow the values to approach the preinfusion values. These results suggest that the optimal ratio of individual BCAA in an amino acid infusion lies between 1:1:1 and 1:2:1 for this injured rat model in total parenteral nutrition.

Amino Acids↗

Effect of the molar ratio of branched-chain to aromatic amino acids on growth and albumin mRNA expression of human liver cancer cell lines in a serum-free medium.

Supplementation of branched-chain amino acids (BCAAs) is often used for the treatment of hepatic encephalopathy and low albuminemia in Japan. In this scenario, although many cases are complicated with hepatocellular carcinoma in chronic viral infection, the effect of BCAA levels on hepatocellular carcinoma cells remains unclear. We investigated the effect of the molar ratios of BCAAs to aromatic amino acids (AAAs) on the growth and albumin mRNA expression of cultured human liver cancer cell lines, HCC-M, HCC-T, PLC/PRF/5, and Hep G2. To exclude the effect of fetal serum in culture media on modification of the growth and albumin transcription of cell lines, we used a synthetic serum-free medium. We found that an increase in the molar ratio of BCAAs to AAAs reduced the growth of Hep G2 cells, and it increased albumin mRNA expression in this cell line at a molar ratio of 0.1-10. These results suggest that the molar ratio of BCAAs to AAAs affect the growth and mRNA expression of some liver cancer cells, and supplementation of BCAAs may at least be beneficial to patients with cirrhosis, even complicated with liver cancer.

Albumins↗

A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data.

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.

Adult↗

Oral branched-chain amino acids do not improve exercise capacity in McArdle disease.

To determine whether oral branched-chain amino acids (BCAAs) improve exercise capacity, six fasting patients with McArdle's disease were given a solution of BCAA (77 mg/kg) or a control noncaloric beverage 30 minutes before exercise. The BCAA meal tripled plasma BCAA levels, increased BCAA catabolism as indicated by greater exercise increases in plasma glutamine and alanine, but lowered mean peak free fatty acid levels and reduced exercise capacity in five of six patients. Lower work capacity may be attributed to a net reduction in muscle fuel availability after BCAA administration.

Administration, Oral↗

Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in hepatic failure.

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1-3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.

Adsorption↗

[An experimental and clinical study of energy-protein metabolism and host defense-repair mechanism in postoperative period--a significance of administration of branched chain amino acid].

The aim of this study is to evaluate in vivo the effect of branched chain amino acid (BCAA). Experimentally, hepatic energy production and protein synthetic rate were measured in gastrectomized rat which was infused BCAA postoperatively. Clinically, following indices were examined in prospectively randomized patients who underwent abdominal operation and were administered with conventional total parenteral nutrition keeping Calorie/N ratio about 150, including nitrogen balance, urinary 3-methylhistidine, retinol binding protein, B lymphocyte percentage and lymphocyte blastogenesis by phytohemagglutinin. Furthermore, plasma BCAA with their keto-analog level, Factor XIII and opsonic activity were determined in another group of patients who received full strength load of BCAA immediately after subtotal or total gastrectomy, in a controlled prospective randomized double-blinded manner. Results obtained from above mentioned measurements exhibited significant improvement by the administration of BCAA. From these findings, it is suggested that BCAA sustains energy-protein metabolism, supports immunocompetence and promotes wound healing under moderately stressed condition where catabolic response is physiologically compensated.

Adult↗

Lack of preventive effect of branched-chain amino acid solution on postoperative hepatic encephalopathy in patients with cirrhosis: a randomized, prospective trial.

The purpose of this randomized, prospective study was to determine whether the infusion of branched-chain amino acid (BCAA)-enriched solution had a preventive effect for treating postoperative hepatic encephalopathy in patients with cirrhosis. Among the 56 patients with cirrhosis, 29 were given BCAA-enriched solution, and 27 were given the conventional amino acid solution for 14 days postoperatively. These groups were indistinguishable with regard to clinical and laboratory criteria at entry, except by sex. The molar ratio of BCAA to aromatic amino acids in the BCAA group was increased postoperatively, whereas the ratio in the control group was decreased, the difference being statistically significant. Among the 29 who received BCAA, three (10.3%) had hepatic encephalopathy; two died and one recovered. Of the 27 control patients, hepatic encephalopathy occurred in three (11.1%); one died and two recovered. There was no significant difference in rate of occurrence of hepatic encephalopathy between the groups. Thus the infusion of BCAA-enriched solution apparently had no preventive effect with regard to hepatic encephalopathy for patients with cirrhosis who underwent surgical treatment.

Amino Acids↗

Basal amino acid concentrations and the response to incremental glucose infusion in tumor bearing rats.

Plasma amino acid concentrations were measured in fasting nontumor bearing (NTB) and tumor bearing (TB; methylcholanthrene induced sarcoma) male Fischer F344 rats during infusion of 0.9% NaCl solution or glucose at 3.72 or 13.05 mumol/100 g total body weight (TBW)/min. The animals were studied when the tumor comprised only 8% of the TBW at a time when decreased food intake and weight loss were not manifest. During 0.9% NaCl infusion there were no significant differences between NTB or TB animals in the concentration of alanine (NTB: 152.6 +/- 20.1; TB: 150.3 +/- 19.0 microM; mean +/- SD), branched chain amino acids (BCAA) (NTB: 343.3 +/- 48.7; TB: 344.2 +/- 20.5 microM), essential amino acids, aromatic amino acids, or total amino acids. During infusion of glucose at 3.72 mumol/100 g TBW/min the alanine levels rose (NTB: 283.6 +/- 33.4; TB: 286.7 +/- 43.3 microM), and the BCAA levels fell (NTB: 215.9 +/- 19.4; TB: 228.7 +/- 43.4 microM) to similar concentrations in both NTB and TB animals. Glucose infusion at 13.05 mumol/100 g TBW/min resulted in an additional increase in the alanine concentration (NTB: 344.5 +/- 28.7; TB: 382.8 +/- 116.6 microM), and a further decrease in the BCAA concentration (NTB: 166.4 +/- 30.8; TB: 160.7 +/- 30.5 microM) without significant differences between NTB and TB animals. Paired analysis for each animal prior to and during glucose infusion demonstrated a similar absolute micromolar change in alanine and BCAA concentration during both glucose infusion rates in both NTB and TB animals. The levels of aromatic amino acids and total amino acids were unchanged and the essential amino acid concentrations were decreased only at the higher glucose infusion rate in both NTB and TB groups. Basal amino acid metabolism appears similar in the NTB and TB animals, prior to the onset of anorexia and weight loss. During exogenous glucose infusion the reciprocal changes in the plasma alanine and BCAA concentrations support the concept of a glucose-alanine-BCAA cycle at the whole body level that appears to respond to a similar extent in NTB and TB animals.

Amino Acids↗

Increased plasma ammonia may inhibit cellular release of branched-chain amino acids in systemic portal encephalopathy.

Plasma amino acid patterns were determined before and after hemofiltration (HF) and hemodialysis (HD) in 6 patients with portal systemic encephalopathy (PSE) and compared with the plasma AA patterns of 16 patients with chronic renal failure (CRF) treated either by HF or HD. The branched-chain amino acids (BCAA) increased paradoxically in PSE patients during HF but not with HD. There were no differences in BCAA's with HF as compared to HD in the CRF patients. The amount of amino acids lost was the same with both treatment modalities and in both patient groups. Much of the amino acids lost were released from the intracellular space. The BCAA release was significantly higher in PSE patients during HF. No correlation was found between plasma insulin, glucagon, and cortisol levels and BCAA release. An inverse correlation was found between the amount of BCAA's released from the intracellular space and the plasma ammonia levels. It is suggested that a selective cellular transport mechanism for BCAA exists which is inhibited by high plasma ammonia levels in PSE.

Adult↗

Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure.

Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mg/kg lipopolysaccaride intravenously and 800 mg/kg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCAA/aromatic amino acid molar ratio of 37.05, 4) BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of 14C-leucine. After the plasma radioactivity of 14C-leucine and the expired 14CO2 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Branched-chain and mixed amino acid solutions and thermogenesis in postoperative patients.

The effect of amino acid composition on the thermogenic response to amino acid infusion was studied in 20 spontaneously breathing postoperative coronary bypass patients and 6 healthy volunteers. On the 1st postoperative day, patients received either a balanced amino acid solution (2510 kJ/24 h) or an amino acid solution consisting primarily (88.8%) of branched-chain amino acids (BCAAs; 2510 kJ/24 h) for 6 h. Another group of patients receiving only hypocaloric glucose served as control subjects. The volunteers randomly received the same balanced amino acid solution (2510 kJ/24 h) or the same BCAA-enriched solution (2510 kJ/24 h) for 6 h. In the coronary bypass patients, both infusion regimens resulted in an increase in resting energy expenditure (REE) (p < 0.01). The thermogenic response to nutrition was 28.5 +/- 5.8 and 46.9 +/- 4.3% (mean +/- SE) in the patients receiving the balanced and BCAA-enriched solutions, respectively (p < 0.05). REE did not change in the control group. Alveolar ventilation increased in both groups (p < 0.05), and the change was more prominent in patients receiving the BCAA-enriched solution. PaCO2 decreased significantly in both nutrition groups. In the healthy subjects, REE increased only during the balanced amino acid infusion (p < 0.05). The thermogenic response to the balanced amino acid solution was 20.7 +/- 4.2% (p < 0.05), whereas no thermogenic response to the BCAA-enriched solution was observed (-5.6 +/- 3.3%, NS). This difference was probably due to the smaller energy cost of BCAA metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effects of prolonged administration of branched-chain amino acids on body composition and physical fitness].

No conclusive data are reported about the effects of long-term branched-chain amino-acids (BCAA) administration on metabolic and respiratory parameters during the sustained hand-grip test (SHGT). Bedside, few data are reported about the relationship between BCAA administration and body composition. Thus, BCAA (14 g/die; 50% L-Leucine, 25% L-Isoleucine, 25% L-Valine) were administered orally to 10 untrained male healthy subjects for 30 days. Before (T0) and after (T1) BCAA administration, oxygen uptake (VO2) and pulmonary ventilation (VE) were evaluated at rest ("baseline", B) and during SHGT. Body height and body weight, body mass index (BMI), fat mass (FM), fat-free mass (FFM), arm muscle area (AMA) and maximal voluntary contraction of forearm muscler (GS, grip strength) were also evaluated at T0 and T1. At T1 FFM increased significantly (T0: 62.3 +/- 7.6 kg; T1: 63.1 +/- 7.5 kg; mean +/- SD; p < 0.05), as well as GS (T0: 46.8 +/- 7.9; T1: 50.6 +/- 7.8; p < 0.01). At T0, VO2 increased significantly during the test (B: 271 +/- 36 ml/min; SHGT: 332 +/- 71 ml/min; p < 0.01), whereas at T1 no significant increase was observed (B: 271 +/- 50 ml/min; SHGT: 286 +/- 60 ml/min). We conclude that the physical fitness of BCAA treated subjects was improved, because of the decrease of O2 uptake during SHGT. Moreover, in our subjects, BCAA seemed to promote FFM-protein synthesis mostly.

Adult↗

Long-term oral administration of branched chain amino acids after curative resection of hepatocellular carcinoma: a prospective randomized trial. The San-in Group of Liver Surgery.

BACKGROUND: Live cirrhosis is a state of protein calorie malnutrition which may induce various complications. This study aimed to elucidate if long-term nutritional support with branched chain amino acids (BCAAs) is effective after hepatic resection for hepatocellular carcinoma (HCC). METHODS: Between 2 and 3 weeks after operation, 75 patients were randomized to receive oral BCAAs (Aminoleban EN) 100 g per day for 1 year, and another 75 patients were assigned to a control group. Mean follow-up times were 35.8 months and 36.0 months respectively. RESULTS: Flapping tremor was less common, body-weight was greater and performance status was better in the BCAA-treated group throughout the 1-year period. BCAA treatment significantly increased red blood cell and serum albumin level in patients with Child grade B and C disease. Substantially similar effects were observed in those with major hepatic resection. Higher Fischer molar ratios were maintained in the treated group. However, there were no differences in cumulative tumour recurrence and survival rates. CONCLUSION: Long-term oral nutritional support with BCAAs after resection of HCC is beneficial in improving clinical features and laboratory data without increasing the rate of tumour recurrence, particularly in patients with advanced cirrhosis or after major hepatic resection.

Administration, Oral↗

Effects of branched-chain amino acids on protein turnover.

Amino acid availability rapidly regulates protein synthesis and degradation. Increasing amino acid concentrations above the levels found in post-absorptive plasma stimulates protein synthesis in a dose-dependent manner at the level of mRNA translation-initiation and inhibits protein degradation by inhibiting lysosomal autophagy. The anabolic effects of insulin on protein synthesis and protein degradation are exerted at the same sites (i.e., peptide chain initiation and lysosomal stabilization) allowing for a rapid synergistic response when both amino acids and insulin increase after a protein-containing meal. In perfused liver preparations, protein anabolic effects are exerted by a group of amino acids acting in concert. The BCAA are among the amino acids required for stimulation of hepatic protein synthesis, but there is no evidence that BCAA or leucine alone are effective. Leucine alone is an important inhibitor of hepatic protein degradation, but maximal inhibition requires in addition several other regulatory amino acids. In heart and skeletal muscle in vitro, increasing the concentration of the three BCAA or of leucine alone reproduces the effects of increasing the supply of all amino acids in stimulating protein synthesis and inhibiting protein degradation. Skeletal muscle is the largest repository of metabolically active protein and a major contributor to total body nitrogen balance. Supplying energy alone (i.e., carbohydrate and lipids) cannot prevent negative nitrogen balance (net protein catabolism) in animals or humans; only provision of amino acids allows the attainment of nitrogen balance. In rats and in humans nourished parenterally, provision of balanced amino acid solutions or of only the three BCAA cause similar improvements in nitrogen balance for several days. There is some evidence that infusions of leucine alone can stimulate muscle protein synthesis in vivo; the effect may be transitory and was not observed by all investigators; provisions of excess leucine alone does not seem to affect total body or muscle protein degradation in vivo. In postabsorptive rats, in vivo, infusion of the three BCAA together stimulates muscle protein synthesis as much as the infusion of a complete amino acid mixture or of a mixture of essential amino acids; the in vivo effect requires coinfusion of glucose or of small (physiological) doses of insulin, suggesting synergism between insulin and amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids, Branched-Chain↗

Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial.

A randomized study was conducted in 37 hospitalized patients at six cooperating hospitals in which protein-intolerant cirrhotic patients were fed increasing amounts of either dietary protein or a branched-chain enriched amino acid solution (BCAA) until they attained an intake of 80 gm protein per day or equivalent or until they developed stage 2 encephalopathy. All patients initially received 20 gm of dietary protein for 1 week, after which 20 gm of protein or BCAA were added weekly. Nitrogen balance improved from negative to positive in all patients in whom it was measured and increased equally in both groups. Seven of the 20 patients in the protein group and 1 of 17 in the BCAA group developed encephalopathy of stage 2 or greater (p less than 0.05). Changes in each component of the portal-systemic encephalopathy syndrome were compared, and differences were statistically significant for mental status grade (p less than 0.01), asterixis (p less than 0.05), Portal-systemic encephalopathy index (p less than 0.01), but insignificant for Number Connection Test, EEG or ammonia. Plasma amino acid profiles showed an increase in BCAA in the study group. Thus, oral BCAA supplements appear to induce positive nitrogen balance to approximately the same degree as an equivalent amount of dietary protein without inducing encephalopathy as frequently.

Adult↗