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PubMed1991

Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids.

Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.

Adult↗
PubMedDate not supplied

Prospective randomized double-blind trial of branched chain amino acid enriched versus standard parenteral nutrition solutions in traumatized and septic patients.

The addition of branched chain amino acids (BCAA) to total parenteral nutrition (TPN) solutions of balanced aminoacid composition has been reported to result in improved nitrogen balance, preservation of plasma protein levels, and improved immune function; however, only a few large clinical studies have been performed, yielding conflicting results. We, therefore, studied in a prospective, randomized double blind trial, the effects of BCAA enrichment of an otherwise isonitrogenous and isocaloric TPN solution on plasma protein levels in 101 traumatized and septic patients. TPN-derived nitrogen intake was similar in both study groups. Nitrogen balances in the BCAA group (n = 49) were not different from those in the standard group (n = 52). Plasma total protein levels increased significantly in the standard group resulting in a significant difference between study groups on day 7. Pre-albumin levels increased significantly in the BCAA group and in the standard group. The number of neutrophils (rods) was significantly lower in the standard group compared to the BCAA group on day 7. Lymphocytes increased significantly in the standard group as did the number of platelets, resulting in a significant difference between study groups on day 7. We conclude that BCAA enrichment of standard TPN solutions does not result in more efficient nitrogen metabolism in septic or traumatized patients.

Amino Acids, Branched-Chain↗
PubMed1985

Use of an intravenous branched chain amino acid enriched diet in the tumor-bearing rat.

The purpose of this study was to determine whether a branched chain amino acids (BCAA) enriched intravenous feeding would have an effect on nitrogen retention in the host tissue, without stimulating tumor growth in the malignant tumor bearing animal. NEDH/c rats with an implanted fibrosarcoma were put on one of two total parenteral nutrition regimens, one of an amino acid formula containing 25 per cent BCAA, by weight and the other containing 50 per cent BCAA. Nitrogen retention in the two tumor-bearing groups was similar, although it was 47 per cent greater than observed in the non-tumor bearing animals (p less than 0.05). Skeletal protein synthesis was significantly reduced by the presence of the tumor in rats on the 25 per cent BCAA formula (from 10.1 per cent/day to 6.1 per cent/day) but was increased to 7.9 per cent/day by the 50 per cent BCAA formula. The BCAA enriched intravenous feeding does not enhance tumor growth and supports skeletal protein synthesis, at least in this experimental model.

Amino Acids, Branched-Chain↗
PubMed1989

Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis.

A study was conducted to investigate the cumulative survival rates among groups of patients with liver cirrhosis who were stratified by plasma branched-chain amino acid (BCAA)/aromatic amino acid (AAA) molar ratio (BCAA/AAA), and to evaluate the effect of long-term oral supplementation with BCAA on the prognosis of cirrhotics with noticeably lower BCAA/AAA molar ratio. When 104 patients with liver cirrhosis were divided into three groups on the basis of BCAA/AAA molar ratio, i.e., BCAA/AAA greater than or equal to 1.8 (Group 1), 1.8 greater than or equal to BCAA/AAA greater than or equal to 1.0 (Group 2), and 1.0 greater than BCAA/AAA (Group 3), Group 1 showed the highest cumulative survival rate, followed, respectively, by Groups 2 and 3 (P less than 0.05). In 20 cases of non-alcoholic liver cirrhosis having BCAA/AAA less than 1.8, oral supplementation with branched-chain amino acid granules (BCAA-G) for 6 months or more (median 27 months, range 7-62 months) brought about significant increase of plasma BCAA concentration, BCAA/AAA molar ratio, and serum albumin concentration. Furthermore, the 20 cases with BCAA-G supplementation showed significantly higher cumulative survival rate during 2-4 years as compared to the control cases matched for age, sex, and etiology (involvement of hepatitis B virus). These findings indicate that long-term oral supplementation with BCAA to cirrhotic patients provides beneficial effect on the prognosis by improving protein malnutritional status and consequently delaying fatal complications such as hepatic failure and gastrointestinal bleeding.

Adult↗
PubMed2003

Evaluation of ammonia metabolism in the skeletal muscles of patients with cirrhosis using N-13 ammonia PET.

OBJECTIVE: Skeletal muscle is said to compensate for the decreased ammonia metabolism in patients with cirrhosis. Branched-chain amino acids (BCAA) are being used as a treatment for hyperammonemia, and are believed to decrease blood ammonia by consumption of BCAA in skeletal muscles. We examined ammonia metabolism of the skeletal muscles in patients with liver cirrhosis after administration of BCAA using 13N-ammonia positron emission tomography (PET). METHODS: The subjects were patients with compensated or decompensated liver cirrhosis. PET studies were performed before and 2 hours after injection of BCAA. Serial dynamic PET scans (2 min x 10 frames) were started simultaneously with 13N-ammonia injection. The standardized uptake value (SUV) of both thighs was calculated. RESULTS: In the patient with compensated liver cirrhosis, there was little difference in the rate of increase in SUV before to after administration of BCAA. However, in the patient with decompensated liver cirrhosis, the rate of increase in SUV after administration was higher than that before administration of BCAA. CONCLUSION: Ammonia metabolism in the muscle of patients with liver cirrhosis could be examined noninvasively under physiological conditions using 13N-ammonia PET. The muscles were found to metabolize ammonia partially, and the role of this contribution to metabolism of ammonia in patients with decompensated liver cirrhosis is particularly important.

Aged↗
PubMed2002

Severe catabolic state after prolonged fasting in cirrhotic patients: effect of oral branched-chain amino-acid-enriched nutrient mixture.

BACKGROUND: Cirrhotic patients frequently undergo various medical procedures, such as diagnostic gastrointestinal endoscopy, without taking breakfast. The aim of the present study was to clarify the effect of longer fasting (> 12 h) on energy metabolism, and to test whether supplementation of an oral branched-chain amino-acid-enriched nutrient mixture (BCAA mixture), which contains various nutrients in addition to BCAA, could improve the catabolic state. METHODS: Metabolic measurement was performed in 30 cirrhotic patients and 13 normal subjects, using indirect calorimetry. RESULTS: Compared with that in the normal subjects, the respiratory quotient (RQ) was significantly lower after an overnight fast in the cirrhotic patients, indicating accelerated fat oxidation and a catabolic state. In addition, RQ in cirrhotic patients (n = 7) decreased rapidly with longer fasting, whereas that in the normal subjects (n = 5) showed relatively stable values. These results indicate that special care should be taken with medical procedures that are carried out in patients who have fasted. The effect of oral glucose, a carbohydrate-rich snack (rice ball), and the BCAA mixture (each, 210 kcal) on RQ was studied in 6 normal subjects and 6 patients with liver cirrhosis after an overnight fast. Supplementation of the carbohydrate-rich snack and the BCAA mixture (210 kcal each) elevated RQ and blood glucose levels to a similar degree in the cirrhotic patients. Oral administration of glucose (210 kcal) led to significantly greater elevation of blood glucose levels than the other snacks, which may be unfavorable for cirrhotic patients, who frequently have glucose intolerance. In the 30 cirrhotic patients, supplementation with the BCAA mixture in the late evening significantly improved RQ in the early morning. CONCLUSIONS: Carbohydrate-rich meals are used as a late evening snack in cirrhotic patients, but our study indicates that supplementation with a BCAA mixture can also be used to reduce fat oxidation in the early morning, with results similar to those with carbohydrate-rich snacks.

Administration, Oral↗
PubMed1988

Effects of branched-chain amino acids on postprandial 3-OH butyrate and glucagon in the baboon.

Although chronic postprandial elevation of branched-chain amino acids (BCAAs) occurs in diabetic subjects and in subjects consuming high-protein diets, the metabolic effects of simultaneously increasing levels of these three amino acids are unclear. In this study, a mixture of the BCAAs was infused intravenously into baboons, beginning 30 minutes after the daily meal and continuing for 200 minutes on four consecutive days. Blood samples were collected on the last day of treatment. Infusion of the BCAAs into fed baboons promoted an increase in peak levels of glucagon, a decrease in postprandial levels of seven amino acids, and an increase in plasma levels of 3-OH butyrate. The ketone body response occurred despite an increase in the plasma ratio of insulin/glucagon in four of the five animals and was not associated with a change in the rate of lipolysis as indicated by plasma glycerol measurements. These findings raise the possibility that ketone bodies are one of the metabolic products of BCAA metabolism induced by high concentrations of leucine or ketoisocaproate. The observation that chronic elevation of BCAAs augments glucagon secretion may explain the parallel increases in plasma glucagon and plasma BCAAs observed in subjects fed high protein diets.

3-Hydroxybutyric Acid↗
PubMed1988

Effect of total parenteral nutrition enriched in branched-chain amino acids on metabolite levels in septic rats.

This study examined the effects of total parenteral nutrition (TPN) enriched with branched-chain amino acids (BCAAs) on metabolite levels of carbohydrate and protein metabolism in septic rats. Results also were obtained for standard amino acid hyperalimentation (conventional TPN). Septic peritonitis was induced in rats by cecal ligation and puncture. Two different experimental models were tested. In one, the two kinds of TPN were administered to the operated rats during the progress of sepsis (the septic phase). In the other, TPN was started immediately after surgical removal of the focal cecum (the recovery phase). The conventional and BCAA-enriched TPN solutions were isocaloric and isonitrogenous except that the percentage of BCAAs in the total amino acids by weight was 35.8% in BCAA-enriched TPN and 20.9% in conventional TPN. On the fifth postoperative day, TPN was discontinued, the animals were killed, and samples of arterial blood, liver, and rectus abdominis muscle were taken. BCAA-enriched TPN had a significant effect on nitrogen balance and survival rate in the septic phase model, and on muscle adenine nucleotide content in both models. Other metabolites showed similar changes in the two TPN groups. These results indicate that BCAA supplement in TPN improves nitrogen balance and peripheral cellular energy status and is thus clinically beneficial in preventive therapy for increased catabolism.

Amino Acids↗
PubMed1992

Branched-chain amino acids increase the seizure threshold to picrotoxin in rats.

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, appetite, and sleep have been reported. The mechanism by which BCAAs exert their effects on CNS remains unclear. Picrotoxin is a proconvulsant drug, acting as an antagonist on the GABA-benzodiazepine receptor complex. Twenty rats were randomized to receive either an IP injection with 4% BCAAs (300 mg/kg; 8 ml/kg) (n = 10) or placebo (saline 8 ml/kg) (n = 10). The mean latency time from injection to onset of seizures was recorded as an indication of the seizure threshold. Latency time was significantly longer for BCAAs than for placebo, 11.2 (+/- 1.9) vs. 8.3 (+/- 1.8) min. Thus, a BCAA injection increased the seizure threshold to picrotoxin (p < 0.03). This suggests that BCAA infusion may exert effects on the GABA-benzodiazepine receptor complex.

Amino Acids, Branched-Chain↗
PubMed1990

Anticatabolic properties of branched chain amino-acids in post-operative patients. A prospective study.

The effect of infusion of branched chain amino-acids (BCAA) on post-operative protein metabolism was analysed in 19 elective surgical patients treated for the first 5 post-operative days with a nutritional regimen of 30 kcal kg(-1) day(-1) and 2 g of amino-acids kg(-1) day(-1). The patients were divided into three groups whose only difference was the amount of BCAA delivered. Our results showed that an increased BCAA input improved nitrogen balance and reduced protein catabolism as estimated by the excretion of 3-methyl-histidine. Since nitrogen retention was maximal during the first 3 post-operative days and the reduction in 3-methylhistidine excretion was observed only on post-operative days 4 and 5, a dual action of BCAA on improving protein synthesis and reducing catabolism is postulated, even though the reduction in catabolism seems to be the main action. This dual action may reflect the unique role of BCAA, which is both 'nutritional' (as they constitute 40% of total amino-acid daily requirements of the healthy subject) and 'pharmacological (as they reduce protein catabolism and improve synthesis in muscle and liver with a dose-dependent effect). Of the three BCAA, isoleucine and leucine seemed to have an 'anticatabolic' effect, whereas an analysis of literature data showed that valine probably has none.

Journal Article↗
PubMed1993

Influence of insulin on peripheral uptake of branched chain amino acids in the 60-hour fasted state.

The influence of insulin on branched chain amino acid (BCAA) metabolism was investigated in healthy subjects faster for 60-64 h, using the euglycemic insulin clamp technique and hepatic venous catheterization. As compared to the postabsorptive state, fasting resulted in a 50-80% decrease in glucose disposal during the clamps, indicating insulin resistance. However, the arterial concentrations of BCAA, which were increased by 200-220% after the fast, decreased to a similar extent during hyperinsulinemia, regardless of the fasting situation. The splanchnic exchange of BCAA was unaltered both in response to fasting itself and to fasting and hyperinsulinemia. The results suggest that insulin resistance during fasting does not influence BCAA metabolism. Furthermore, the changes in BCAA concentrations after a prolonged fast are due to altered peripheral metabolism of BCAA.

Journal Article↗
PubMed2004

Branched-chain amino acids, hepatocyte growth factor and protein production in the liver.

Although the functions associated with differentiation are thought to be suppressed when cells proliferate, recent studies have shown that several mitogens can stimulate functions such as protein production under certain physiological conditions. Hepatocyte growth factor (HGF) is now considered to be a pluripotent factor and has been shown to stimulate the differentiated functions of hepatocytes, as well as their proliferation. The use of HGF for the treatment of liver disease, especially hepatic failure, has been suggested. Because patients with decompensated liver cirrhosis have decreased plasma concentrations of branched-chain amino acids (BCAAs), many investigations in laboratory animals and patients have been designed to demonstrate the benefits of supplementation of BCAAs on the hepatic metabolism of proteins. However, the mechanisms involved in the specific actions of BCAAs remain to be elucidated. Amino acids are molecules that modulate numerous cellular functions. BCAAs are known to influence gene expression, cellular metabolism, amino acid transport, and protein turnover. In this paper, we show the potential of BCAAs for stimulating HGF synthesis in the liver and discuss the possibility that BCAAs stimulate protein production by hepatocytes through the induction of HGF.

Journal Article↗
PubMed2004

Effects of liver failure on branched-chain alpha-keto acid dehydrogenase complex in rat liver and muscle: comparison between acute and chronic liver failure.

BACKGROUND/AIMS: Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyses the committed step in the branched-chain amino acid (BCAA) catabolic pathway. In many cases of liver failure, the serum BCAAs/aromatic amino acids ratio (Fisher's ratio) decreases, and BCAAs have been administered to patients with liver failure to correct this ratio. We conducted an animal study to examine whether the effects on hepatic BCKDH complex differ between acute liver failure (ALF) and chronic liver failure (CLF). METHODS: ALF and CLF was induced in rats by a single high-dose injection and 21 weeks of repeated low-dose injections of carbon tetrachloride, respectively. Plasma BCAA and branched-chain alpha-keto acid (BCKA) levels, and activities and protein amounts of hepatic BCKDH complex and kinase were measured. RESULTS: ALF was characterized by elevated plasma BCAA and BCKA levels and decreased hepatic BCKDH activity. CLF was characterized by decreased plasma BCAA and BCKA levels and increased hepatic BCKDH activity. This increase in BCKDH activity in CLF was associated with the decreased BCKDH kinase, which is responsible for the BCKDH inactivation. CONCLUSIONS: The results obtained in the present study suggest that BCAA catabolism is suppressed in ALF and increased in CLF.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1984

[Effects on muscular and general proteolysis in burn patients of a solution enriched with branched amino acids].

In order to assess the effects of a branched chain amino acid (BCAA) enriched solution on urinary nitrogen loss and muscle protein breakdown, 22 burnt patients were randomly divided into two groups immediately after hospital admission: 11 patients received a 22% BCAA amino acid solution, 11 patients received a 41% BCAA amino acid solution. Nitrogen intake was 0.2 g per day during the first 4 days in each group. Urinary total nitrogen, urinary creatinine and urinary 3,methylhistidine (3,MeHis) were measured for 4 days. Nitrogen balance, 3,MeHis/nitrogen ratio and 3,MeHis/creatinine ratio were calculated in each group. The two groups were compared using Student's test. Nitrogen, creatinine and 3,MeHis urinary excretion, and nitrogen balance were not significantly different in the two groups, except for urinary nitrogen on day 3 which was slightly higher in the 41% BCAA group. The 3,MeHis/nitrogen ratio on day 1, day 2 and during the whole study period, as well as the 3,MeHis/creatinine ratio on day 2, were significantly lower in the 41% BCAA group. These results were in agreement with a decrease in muscle/whole body urinary nitrogen excretion. However, no beneficial effect upon nitrogen loss or nitrogen balance was shown by using the 41% BCAA rich amino acid solution.

Adolescent↗
PubMed1998

Oral supplementation with branched-chain amino acids improves survival rate of rats with carbon tetrachloride-induced liver cirrhosis.

We investigated whether supplementation with branched-chain amino acids (BCAA) improves survival of rats with carbon tetrachloride (CCl4) -induced cirrhosis. Liver cirrhosis was induced in 40 male Sprague-Dawley rats by administering CCl4 for 15 weeks. Twenty rats each were then assigned to the control and BCAA group and fed a casein diet or a BCAA-supplemented casein diet, respectively, for an additional 17 weeks with repeated injections of CCl4. No significant difference occurred in either mean energy or nitrogen intake or in body or liver weight between the two groups. BCAA-supplementation significantly preserved plasma albumin concentrations (P < 0.05) and inhibited significantly the occurrence of ascites and hyperammonemia (P < 0.05). The survival rate was significantly higher in the BCAA group (P=0.03), while no significant difference was found in liver histology between the groups. These results suggest that BCAA improved survival of rats with CCl4-induced cirrhosis by preventing hypoalbuminemia and hyperammonemia without directly reducing hepatic necrosis and fibrosis.

Administration, Oral↗
PubMed1998

Role of branched-chain aminotransferase isoenzymes and gabapentin in neurotransmitter metabolism.

Because it is well known that excess branched-chain amino acids (BCAAs) have a profound influence on neurological function, studies were conducted to determine the impact of BCAAs on neuronal and astrocytic metabolism and on trafficking between neurons and astrocytes. The first step in the metabolism of BCAAs is transamination with alpha-ketoglutarate to form the branched-chain alpha-keto acids (BCKAs). The brain is unique in that it expresses two separate branched-chain aminotransferase (BCAT) isoenzymes. One is the common peripheral form [mitochondrial (BCATm)], and the other [cytosolic (BCATc)] is unique to cerebral tissue, placenta, and ovaries. Therefore, attempts were made to define the isoenzymes' spatial distribution and whether they might play separate metabolic roles. Studies were conducted on primary rat brain cell cultures enriched in either astroglia or neurons. The data show that over time BCATm becomes the predominant isoenzyme in astrocyte cultures and that BCATc is prominent in early neuronal cultures. The data also show that gabapentin, a structural analogue of leucine with anticonvulsant properties, is a competitive inhibitor of BCATc but that it does not inhibit BCATm. Metabolic studies indicated that BCAAs promote the efflux of glutamine from astrocytes and that gabapentin can replace leucine as an exchange substrate. Studying astrocyte-enriched cultures in the presence of [U-14C]glutamate we found that BCKAs, but not BCAAs, stimulate glutamate transamination to alpha-ketoglutarate and thus irreversible decarboxylation of glutamate to pyruvate and lactate, thereby promoting glutamate oxidative breakdown. Oxidation of glutamate appeared to be largely dependent on the presence of an alpha-keto acid acceptor for transamination in astrocyte cultures and independent of astrocytic glutamate dehydrogenase activity. The data are discussed in terms of a putative BCAA/BCKA shuttle, where BCATs and BCAAs provide the amino group for glutamate synthesis from alpha-ketoglutarate via BCATm in astrocytes and thereby promote glutamine transfer to neurons, whereas BCATc reaminates the amino acids in neurons for another cycle.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2004

Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs.

The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 micromol leucine, 0.640 micromol isoleucine and 0.693 micromol valine/min.kg); (3) 18.7 micromol glucose/min.kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine (Phe) as follows: (1) L-[1-13C]Phe; (2) L-phenyl-[ring 2H5]-alanine; (3) L-[15N]Phe; (4) L-[ring 2,6-3H]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, Ks was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on Ks compared with control sheep. Ks was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in Ks in muscle of growing ruminant animals.

Amino Acids, Branched-Chain↗
PubMed1998

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: In patients with mild LC, BCAAs caused a significant increase in glucose level (maximal increment, 12.5+/-2.5 mg/dl) with a great increase in insulin (maximal increment, 39.5+/-8.3 microU/ml) and a small increase in glucagon secretion (maximal increment, 101.0+/-16.0 pg/ml). In patients with advanced LC, BCAAs caused a great increase in glucagon secretion (220.5+/-19.4 pg/ml) with only a slight increase in glucose levels (5.8+/-2.2 mg/dl). CONCLUSION: BCAAs solution causes hyperglycemia in mild LC due to insulin resistance, whereas it causes only a slight increase in severe LC due to hepatic glucagon resistance. Thus, there is a possibility that BCAAs solution may lead to hypoglycemia in advanced LC with hepatic glycogen depletion.

Adult↗