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[A clinical study of amino acid metabolism in cancerous hypoproteinemia--the role of branched chain amino acids (BCAA) and appropriate compositions of BCAA in parenteral nutrition].

In order to determine the nutritional effects of BCAA compositions in the treatment of cancerous hypoproteinemia, the appropriate ratio of I-leu: Leu: Val and the proportion of BCAA to Total Amino Acids were investigated. As for results, indices such as the serum albumin, the RBP and N-balance quickly recovered to normal levels when the ratio of I-leu: Leu: Val was 1.0:1.8:1.0 and the proportion o BCAA to TAA was 31%. These composition thus may be suitable for the treatment of cancerous hypoproteinemia.

Amino Acids

[A study of adequate energy, amino acid, and carbohydrate requirements in postoperative total parenteral nutrition--the effect of branched chain amino acid (BCAA) and carbohydrate mixture of glucose, fructose, and xylitol (GFX)].

This study was performed to elucidate adequate energy and amino acid (AA) requirements for TPN patients after abdominal surgery. The effects of AA formula, rich in BCAA (30% BCAA), as a nitrogen source and the carbohydrate mixture of glucose, fructose, and xylitol (GFX = 4:2:1), on nitrogen sparing were also studied. Forty-nine patients having undergone major abdominal surgeries, were divided into 5 groups. The regimens were as follows: G1: 40kcal/kg, standard amino acid (21% BCAA) 1.5g/kg. day, G2: 40kcal/kg, 30% BCAA 1.5g/kg.day, G3: 30kcal/kg, 21% BCAA 1.5g/kg.day, G4: 30kcal/kg, 30% BCAA 1.5g/kg.day, G5: 40kcal/kg, 21% BCAA 1.5g/kg.day. Glucose was the sole carbohydrate energy source in G1 through G4. In G5, GFX was used. (1) Accumulated nitrogen balances during the week immediately after operation were significantly higher in G1 and G2 where higher energy intakes were administered than G3 and G4. (2) The nitrogen balances during the 2nd or 3rd postoperative days in G2 or G4, using 30% BCAA as a nitrogen source, were higher than in G1 or G3 respectively. (3) The changes in serum rapid turnover proteins were not significantly different among these groups. (4) The accumulated nitrogen balance in G5 tended to be higher than that of G1. These results indicate that BCAA rich amino acid formula will induce a more favorable nitrogen sparing effect than a conventional AA formula on TPN patients under surgical stress.

Adult

Effect of glucose and branched chain amino acid (BCAA) infusion on onset of liver regeneration and plasma amino acid pattern in partially hepatectomized rats.

Immediately after 70% hepatectomy, rats were infused via the jugular vein with one of the following solutions: saline, 3% or 8% glucose solution, 3% BCAA solution, 8% Nutramin (17% BCAA) or 8% Nutramin enriched with BCAA (47% BCAA). Rats were killed 18, 21, 24 and 30 h after partial hepatectomy. The course of liver regeneration was assessed from incorporation of labeled thymidine into DNA and from hepatocyte mitotic activity. After partial hepatectomy a decrease of glycemia and increase of plasma phenylalanine concentrations were observed. Glucose infusion had a pronounced inhibiting effect on the onset of liver regeneration. The decreased incorporation of labeled thymidine into DNA and the decreased hepatocyte mitotic activity in glucose-infused rats were associated with higher plasma concentrations of tyrosine and phenylalanine. Parenteral administration of 3% BCAA solution and 8% Nutramin enriched with BCAA had a favourable effect on the onset of liver regeneration after partial hepatectomy compared with glucose- and Nutramin-infused groups. In BCAA-infused rats elevated levels of BCAA and decreased concentrations of tyrosine and phenylalanine were noted.

Amino Acids

Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.

Administration, Oral

Failure of BCAA supplementation to promote nitrogen retention in injured patients.

The purpose of this study was to determine if supplementing total parenteral nutrition (TPN) with lipids or the branched chain amino acids (BCAA) leucine, isoleucine, and valine influences nitrogen balance in the injured patient. Four TPN study solutions were used, with each patient receiving two of the solutions for 4 days each. Group A received solutions consisting of 19% and 44% BCAA, with nonnitrogen calories supplied by 100% carbohydrate. Group B received a 7:3 carbohydrate-to-lipid ratio of nonnitrogen calories as a fuel source. Neither BCAA supplementation nor varying fuel substrates promoted a difference in nitrogen retention. The added cost of BCAA supplementation, along with the lack of an effect upon nitrogen accretion, indicates that greater benefits must be demonstrated before widespread use of BCAA supplementation can be recommended in the injured patient.

Amino Acids, Branched-Chain

[Effect of branched chain amino acid (BCAA) enriched solution in postoperative patients receiving TPN].

Validity of branched chain amino acid (BCAA) enriched solution in surgical stress was assessed using total catecholamine excretion (U-CA) as the severity in dex. Thirty percent BCAA solution was infused no 21 patients (T group), and 21% BCAA to 18 patients (P group) pre and postoperatively. 2.0 g protein and 35 kcal/kg.day were provided by total parenteral nutrition (TPN). Correlation of nitrogen-balance to U-CA was statistically significant in both groups (p less than 0.01). The difference of correlations was statistically significant when analyzed by covariance (p less than 0.05). Rapid turnover proteins were significantly higher in T group, but no difference of urinary 3-methylhistidine excretion was observed. Increased uptake of BCAA and release of glutamine and alanine by skeletal muscle were observed. However, no alteration in arterio-venous difference of phenylalanine and tyrosine was detected. In conclusion, 30% BCAA solution significantly improved postoperative protein metabolism, probably due to the improved visceral protein metabolism supported by amino acid supply by skeletal muscle.

Amino Acids, Branched-Chain

Pharmacological reversal of abnormal glucose regulation, BCAA utilization, and muscle catabolism in sepsis by dichloroacetate.

Sepsis has been shown to decrease skeletal muscle glucose oxidation by inhibiting the pyruvate dehydrogenase activity (PDHa) and to increase proteolysis and use of branched-chain amino acids (BCAA). The effects of dichloroacetate (DCA), which reverses PDHa inhibition, were studied in skeletal muscle from a septic (S) rat model of intra-abdominal abscess (E. coli + B. fragilis) and compared to control (C) and sterile inflammatory abscess (I) animals. In one set of S, I, and C animals, DCA (1 mmol/kg) was injected intraperitoneally at 0, 30, and 60 min. Septic, but not I, rats had a twofold increase in skeletal muscle lactate concentrations over C, but no changes in pyruvate. After DCA, both lactate and pyruvate were reduced (p less than 0.001) to same level in S, I, and C. Skeletal muscle alanine was increased in S compared to I or C, but after DCA was reduced threefold in C, S, and I (p less than 0.001) suggesting that alanine synthesis may be impaired due to decreased pyruvate availability. Like alanine, skeletal muscle BCAA were increased in S compared to C, but not altered in I. Following DCA, BCAA levels in muscle from S were reduced (p less than 0.001) to values seen in C or I. Muscle phenylalanine content was significantly elevated in S (p less than 0.05) compared to C or I, but was reduced (p less than 0.05) after DCA in S but not in C or I. Decreased muscle phenylalanine associated with lowered BCAA suggests DCA may decrease septic muscle protein catabolism and/or enhance protein synthesis. Coupled with an increased PDHa and reduced lactate levels, this suggests that DCA may reverse the excess muscle catabolism and BCAA dependence of sepsis by increasing glucose and lactate oxidation and may be a useful therapeutic modality.

Acetates

Administration of balanced or BCAA-enriched amino acid solution in septic rats. Effects on protein synthesis in the liver.

Total hepatic protein synthesis was measured in vivo with a flooding-dose technique, and the production of total secreted proteins, albumin, complement component C3, and seromucoid fraction was measured in perfused livers of septic rats that received one of three different solutions infused intravenously; Group 1 received 16.4% dextrose; Group 2 received Aminosyn (25% BCAA) in 10.6% dextrose, and Group 3 received Freamine HBC (45% BCAA) in 10.6% dextrose. All solutions were isocaloric, and the amino acid solutions were isonitrogenous. The solutions were administered for 18 or 48 hours after the induction of sepsis. There were no significant differences in mortality rates in the three treatment groups. The negative nitrogen balance seen in the dextrose-infused animals was reversed to the same degree by the two different amino acid solutions. There were no significant differences in hepatic protein synthesis rates in vivo between the three groups of rats. Synthesis rates of secreted proteins in perfused liver were similar in the different treatment groups in the 18-hour experiments, whereas in the 48-hour experiments, synthesis rates of total secreted proteins, C3, and the serumucoid fraction were higher in Group 1 than in Groups 2 and 3. The results suggest that administration of an amino acid solution improves nitrogen balance in sepsis, but that this effect is not caused by stimulated hepatic protein synthesis. The nitrogen-sparing effect during sepsis of a branched chain amino acid (BCAA)-enriched solution does not seem to be superior to that of a balanced amino acid solution.

Amino Acids

[Metabolic effects of GFX+BCAA solution in the old aged rats after operation].

Effects of total parenteral nutrition (TPN) on the perioperative metabolism in old aged rats were evaluated. Extremely old rats (over 100 weeks old) and young rats undergoing laparotomy were treated with TPN (200 ml/kg/days, 182 cal/kg/day, 148 nonprotein cal/N ratio) consisting of carbohydrate mixtures (combination of glucose, fructose, and xylitol, 4:2:1 GFX solution) and 10% amino acids solution with 30% of branched chain amino acids (BCAA). Blood, liver, and urine samples were analyzed on 1, 3 postoperative days. Increased body weight, positive balance in daily nitrogen excretion, and decreased water content of the liver were observed in old rats. Protein, glycogen, and triglyceride contents of the liver tissue increased in old rats. However the young rats showed negative nitrogen balance and stronger catabolic effect than the old rats. It suggested negative nutritional balance in young rats with this decreased dosage of GFX+BCAA solution suitable for the old rats. In conclusion, decreased amounts of GFX+BCAA solution improved perioperative metabolism in the extremely old.

Age Factors

Amino acid (GAS:BCAA) ratios in plasma and gut contents of short-term protein depleted rats.

The ratio of total concentrations or molar ratios (moles/1,000 amino acid residues) of three non-essential amino acids (glycine, alanine, serine-GAS) and three essential-branched chain amino acids (valine, isoleucine, leucine-BCAA) were investigated in rat systemic and portal vein plasma and jejunal and ileal gut contents after feeding normoprotein (NP) or protein-free (PF) diets for 7 days. Amino acid analysis of gut content showed that the GAS:BCAA ratio was not significantly altered by the PF diet either in the jejunum or in the ileum. On the contrary, the PF diet, caused a three and four-fold increase in this ratio in the portal and systemic plasma, respectively. The situation was produced by the higher concentrations of GAS, which remained near control levels (portal plasma) or exceeded these values (systemic plasma), in contrast to the decreasing levels of BCAA found in both plasmas of the PF group.

Amino Acids

[The behavior of visceral proteins in digestive surgery patients undergoing total peripheral parenteral nutrition enriched with branched-chain amino acids (BCAA)].

The objective of this study, is to confirm a clear benefit of protein synthesis after administration of branched amino acids in parenteral nutrition solutions. Particularly, on a parenteral total hypocaloric nutrition including lipids. Eighty one digestive surgical patients, were included in this study. Fifty with neoplastic disease and thirty one without. Patients in both study groups received a similar peripheral vein nutritional support regimen one week after surgical treatment. To evaluate the effects of the branched chain amino acid enrichment on total parenteral nutrition, we observed the behavior of short middle life proteins such as transferrin, prealbumin, and retinol binding protein, for their reliability as indexes of protein synthesis.

Amino Acids, Branched-Chain

Human brown fat metabolism associates with systemic branched-chain amino acids homeostasis.

Circulating branched-chain amino acids (BCAAs) are linked with insulin resistance, but the human tissues contributing to systemic BCAA homeostasis remain incompletely defined. Brown adipose tissue (BAT) is a metabolically active adipose depot associated with favourable insulin sensitivity, yet its role in BCAA metabolism in humans remains unclear. We tested whether human BAT metabolism is associated with circulating BCAA levels, BAT-resident BCAA-catabolic signatures, and longitudinal changes in systemic BCAA homeostasis. We studied 83 adults who underwent metabolic phenotyping, PET-CT assessment of cold-stimulated BAT metabolism, and serum metabolomic profiling at room temperature and during acute mild cold exposure. Supraclavicular BAT biopsies from 25 participants were analysed by transcriptomics and metabolomics, and 40 participants were re-examined for circulating BCAA profiles after approximately five years. Participants with high BAT metabolism had lower circulating BCAA levels than those with low BAT metabolism. Within BAT, metabolically active individuals exhibited lower relative BCAA abundance together with higher expression of genes involved in BCAA catabolism. These BAT BCAA-catabolic signatures aligned with thermogenic capacity and indices of systemic insulin sensitivity. In contrast, individuals with low BAT metabolism showed increases in circulating BCAAs over five years. Integrative analyses further linked circulating lipopolysaccharide, a marker of metabolic endotoxemia, with higher BAT BCAA and aminomalonate abundance, together with transcriptional patterns involving inflammatory and mitochondrial pathways. Together, these findings identify human BAT metabolism as a tissue phenotype linked to systemic BCAA homeostasis and extend the role of human BAT beyond thermogenesis, suggesting that BAT-associated BCAA handling may contribute to systemic metabolic health.

Humans

Nutritional effects of branched-chain amino acids on injured rats in total parenteral nutrition.

In this study, we investigated the optimal contents of branched-chain amino acids (BCAA) in a balanced amino acid infusion in laparotomized rats. The BCAA contents of four infusion solutions used were prepared to 22, 31, 40, and 49% of total amino acids, respectively. The amounts of essential amino acids except for BCAA were equal in all the solutions. Rats weighing about 240 g were infused with about 200 mg of nitrogen and 10 g of glucose daily for 7 days and evaluated for body weight change, nitrogen balance, plasma and urinary amino acid levels, and plasma constituent levels. The body weights of all the groups were approximately maintained during the infusion period. The nitrogen balance of the BCAA-31 group was more positive than that of the BCAA-22 group and was not different from those of the BCAA-40 and BCAA-49 groups. Plasma total-protein level of the BCAA-31 group was higher than that of the BCAA-22 group and was equal to those of the BCAA-40 and BCAA-49 groups. Even when the BCAA content in an amino acid infusion was increased, no abnormal elevation was observed in plasma BCAA levels. There were no differences in the other nutritional parameters among the four infusion groups. These results suggest that the BCAA contents in an amino acid infusion are enough at 31% of total amino acids for this injured rat model.

Amino Acids, Branched-Chain

Dietary branched-chain amino acids and protein selection by rats.

Consumption by rats of high protein diets is associated with elevated plasma and brain concentrations of branched-chain amino acids (BCAA). We examined the possibility that changes in BCAA concentrations in blood and brain might serve as modulators of protein consumption. After young rats had adjusted to selecting between a 10% or 25% casein diet and a 50% casein diet, a mixture of BCAA was included in the diet containing the lower amount of protein (10% + BCAA, 25% + BCAA). Supplementation of the 10% or 25% casein diets with BCAA and subsequent elevation of BCAA concentrations in plasma and brain were associated with increased selection of protein in rats given the 10% + BCAA/50% casein diet choice, but not in rats offered the 25% + BCAA/50% casein diets. When no alternative diet was available, addition of BCAA to a 15% casein diet depressed food intake, and rats given a choice between a 15% casein diet with or without added BCAA selected almost exclusively the diet without added BCAA. Although BCAA concentrations were high in plasma and brain in all experiments, concentrations of methionine, tyrosine, phenylalanine, tryptophan and histidine were low in brain in experiments in which rats altered their diet or protein selection after BCAA addition. High concentrations of BCAA in plasma and brain were not consistently associated with changes in protein selection.

Amino Acids