Infusion Of Branched-chain Amino Acids Research Articles

Effects of branched-chain amino acids on placental amino acid transfer and insulin and glucagon release in the ovine fetus

Objective: Competition for placental amino acid transporters can affect the fetal supply of amino acids. Specifically, the branched-chain amino acids—isoleucine, leucine, and valine—may inhibit the transfer of other amino acids. This study was undertaken to determine the effect of branched-chain amino acids on the umbilical uptake of amino acids. Study Design: Six late-gestation ewes were infused sequentially for 2 hours with 3 different mixtures of amino acids: (1) one that was comparable to commercial parenteral nutrition preparations, (2) the same solution without branched-chain amino acids, and (3) branched-chain amino acids alone. Maternal and fetal blood samples were collected simultaneously for the determination of uterine and umbilical uptake values of amino acids, and for concentrations of arterial insulin, glucagon, glucose, and lactate before (control) and during (experimental) infusion. Results: Umbilical uptake of branched-chain amino acids increased significantly when they were present in the infusates. The fetal uptake of several other amino acids could be increased by increasing their maternal concentrations. Inhibition of umbilical uptake by branched-chain amino acids could be shown for threonine and methionine. The infusion of branched-chain amino acids alone did not affect maternal and fetal insulin or glucagon concentrations. Conclusions: In late-gestation sheep, an increase in maternal plasma concentration of branched-chain amino acids led to increased branched-chain amino acid umbilical uptake, but branched-chain amino acids can also inhibit the transport of some amino acids to the fetus. Changes in fetal plasma concentration and uptake of branched-chain amino acid appear to have no significant effect on fetal insulin or glucagon. (Am J Obstet Gynecol 2001;185:487-95.)

Branched chain amino acids activate messenger ribonucleic acid translation regulatory proteins in human skeletal muscle, and glucocorticoids blunt this action.

Branched chain amino acids (BCAA) are particularly effective anabolic agents. Recent in vitro studies suggest that amino acids, particularly leucine, activate a signaling pathway that enhances messenger ribonucleic acid translation and protein synthesis. The physiological relevance of these findings to normal human physiology is uncertain. We examined the effects of BCAA on the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (eIF4E-BP1) and ribosomal protein S6 kinase (p70(S6K)) in skeletal muscle of seven healthy volunteers. We simultaneously examined whether BCAA affect urinary nitrogen excretion and forearm skeletal muscle protein turnover and whether the catabolic action of glucocorticoids could be mediated in part by inhibition of the action of BCAA on the protein synthetic apparatus. BCAA infusion decreased urinary nitrogen excretion (P < 0.02), whole body phenylalanine flux (P < 0.02), plasma phenylalanine concentration (P < 0.001), and improved forearm phenylalanine balance (P = 0.03). BCAA also increased the phosphorylation of both eIF4E-BP1 (P < 0.02) and p70(S6K) (P < 0.03), consistent with an action to activate the protein synthetic apparatus. Dexamethasone increased plasma phenylalanine concentration (P < 0.001), prevented the BCAA-induced anabolic shift in forearm protein balance, and inhibited their action on the phosphorylation of p70(S6K). We conclude that in human skeletal muscle BCAA act directly as nutrient signals to activate messenger ribonucleic acid translation and potentiate protein synthesis. Glucocorticoids interfere with this action, and that may be part of the mechanism by which they promote net protein catabolism in muscle.

Insulin Stimulates Phenylalanine Uptake across the Hind Limb in Fed Lambs

Five lambs ( approximately 6 mo of age and 30 kg), with an external iliac artery and vein catheterized and fed to maintain body weight, were used to examine effects of close arterial infusion of insulin and branched-chain amino acids (BCAA) on net phenylalanine (Phe) uptake across the hind limb. Treatments, administered randomly on five consecutive days to each lamb, were 400 min infusions of: i) saline (control); ii) insulin to double iliac artery concentration (low insulin); iii) as ii but to quadruple insulin concentration (high insulin); iv) 30 micromol/min leucine and 22.5 micromol/min each isoleucine and valine (BCAA) and v) co-infusion of ii and iv. Blood was sampled over the last 200 min from the iliac vein and right ventricle of the heart. High insulin caused a slight decrease (-13%, P < 0.05) in systemic glucose concentration, but did not alter systemic insulin concentration. Insulin, at both doses and in combination with BCAA, resulted in 9-fold greater net Phe uptake (P < 0.05) than the control, as did BCAA alone. Because BCAA alone increased net Phe uptake, these may have stimulatory effects directly or may enhance endogenous insulin. Maximum stimulation was achieved with low insulin because there was no increase in net Phe uptake with high insulin or from co-infusion with BCAA. Insulin, at low concentrations, may be important to growth in animals with marginal nutrition.

Effects of branched-chain amino acids and sodium caseinate on milk protein concentration and yield from dairy cows.

Our study investigated the separate and combined effects of branched-chain amino acids (AA) and sodium caseinate on milk protein concentration and yield. Four Holstein cows (112 d in milk) were abomasally infused with water, branched-chain AA (150 g/d), sodium caseinate (600 g/d), or branched-chain AA plus sodium caseinate (44 and 600 g/d, respectively) according to a 4 x 4 Latin square design with 8-d treatment periods. Cows were fed a dry diet based on alfalfa hay and concentrates for ad libitum intake. The ration was formulated to exceed requirements for metabolizable energy and protein using the Cornell Net Carbohydrate and Protein System. Neither daily dry matter intake (24.2 +/- 0.4 kg/d; X +/- SEM) nor milk yield (32.9 +/-; 0.4 kg/d) was affected by any of the infusion treatments. Infusion of branched-chain AA had no effect on any milk production parameters, despite a 50% increase in their concentrations. Modest increases in milk protein concentration (0.1%) and milk protein yield (62 g/d) resulted from the infusion of sodium caseinate or branched-chain AA plus sodium caseinate. True protein and whey protein concentrations in milk were also marginally increased by infusion of sodium caseinate and branched-chain AA plus sodium caseinate, and infusion of branched-chain AA, sodium caseinate, or both elevated milk nonprotein N content. Plasma urea N concentrations were elevated by the sodium caseinate and branched-chain AA plus sodium caseinate treatments. No treatment effects on other plasma metabolites or hormones were observed. Our results show no benefit of supplementation with branched-chain AA and only modest effects of sodium caseinate on milk protein concentration and yield in well-fed cows.

Insulin stimulates phenylalanine uptake across the hind limb in fed lambs

Although insulin has been shown to stimulate muscle protein accretion in nonruminants (e.g., Wray-Cahen et al., 1998) evidence for this same effect in ruminants has been equivocal (e.g., Oddy et al., 1987; Wolff et al., 1989). Moreover, when insulin has been reported to have an anabolic effect in ruminants, the animal has been in the fasted state. In addition, Garlick and Grant (1988) have shown that branched-chain amino acids (BCAA) enhanced insulin-stimulated protein synthesis in fasted rats. The primary aim of the present study was to ascertain whether insulin increases phenylalanine (Phe) uptake (used as an index of skeletal muscle protein anabolism) across the hind limb of fed lambs. A secondary aim was to determine if infusion of BCAA, alone or in combination with insulin, would stimulate Phe uptake greater than insulin alone.

Role of tryptophan in the elevated serotonin-turnover in hepatic encephalopathy.

The increase of the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased turnover of serotonin (5-HT). To study the role of tryptophan on the increased brain 5-HT metabolism in HE, we attempted to monitor brain levels of tryptophan in rats with thioacetamide-induced acute liver failure by intravenous infusion of branched-chain amino acids (BCAA). The effect of this treatment on 5-HT synthesis and metabolism was investigated in five brain areas. BCAA-infusions (1 and 2 gm/kg/24 h) increased the ratio BCAA/aromatic amino acids in plasma two- and fourfold, respectively, and lowered both plasma and brain levels of tryptophan. At the higher BCAA-dose all parameters suggesting an altered brain 5-HT metabolism (increased brain levels of 5-HT and 5-HIAA, increased 5-HIAA/5-HT ratio) were almost completely normalized. These results provide further evidence for the role of tryptophan in the elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE.

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

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

Clinical economics review: nutritional support.

Nutritional support currently accounts for about 1% of the total health care costs in the USA. Interestingly, most of the prospective randomized controlled trials to date have not been able to demonstrate that this therapeutic intervention alters morbidity or mortality. In fact, parenteral nutritional support may predispose the recipients to developing systemic infections. There have been a few areas in which nutritional support may be of benefit. Enteral supplements given to underweight women who suffer hip fractures reduce the hospital stay and, presumably, overall cost. Preoperative parenteral nutritional support may produce a small absolute reduction in post-operative morbidity, but its cost becomes prohibitive. Preoperative enteral nutritional support, especially if carried out in the home, may be of benefit (using the most optimistic interpretation of a small number of trials); if so, it is an economically defensible intervention. Particular nutrients or diets may have specific effects on certain disease processes. Indirect comparisons have suggested that elemental diets can be used to treat flares of Crohn's disease (perhaps because putative food antigens are removed). However, corticosteroid therapy is more efficacious. Furthermore, it is less expensive to employ 6-mercaptopurine as the next modality in steroid failures. Branched-chain amino acid infusions may have some effect on hepatic encephalopathy, but again, lactulose is less expensive. Nutritional support is one area of medicine in which there has been far more enthusiasm than the data justify. Disease-associated malnutrition probably is a secondary phenomenon, not an important cause of morbidity. The widespread use of this modality cannot be justified in a cost-constrained health care system.

Effect of Branched-Chain Amino Acids(BCAA) on the Ventilatory Response to Hypoxia in Newborn Piglets. † 1481

The administration of BCAA produces a significant increase in basal ventilation and CO2 response in adult humans and significant decrease in apneic episodes in premature infants. In order to assess the effect of BCAA on the neonatal ventilatory response to hypoxia, 13 sedated and spontaneously breathing piglets £7 days old were studied before and after a 4 hour infusion of 53% BCAA (n = 8) or 5% dextrose (D5W; n =5) solution. Minute ventilation (VdotE), oxygen consumption (VdotO2), arterial blood pressure (ABP), heart rate (HR), and arterial blood gases were measured in room air (RA) and during 1, 5 and 10 min of hypoxia (FiO2 = 0.10). Mean ± SD of absolute values and% change (Δ) from RA for VdotE (ml/kg/min) were as follows: Table Although a similar increase in VdotE occurred at 1 min of hypoxia pre- and post-BCAA, a significant increase in the ventilatory response at 5 and 10 min of hypoxia was noted post-BCAA. A significant increase in respiratory rate(p<0.002) and decrease in PaCO2 (p<0.004) were also observed after BCAA infusion. Changes in VdotO2, ABP, HR, pH, PaO2 and base excess with hypoxia were not different between pre- and post- BCAA. In the control group, the cardiorespiratory response to hypoxia was not modified by D5W infusion. These data suggest that the administration of BCAA increases central respiratory output and eliminates the ventilatory depression observed during sustained hypoxia in the neonate.

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 14CO 2 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. Breakdown was not suppressed with any solution. These results suggest that rats with AHF are in a catabolic state and that any of the three amino acid solutions can be oxidized to provide energy in AHF. In addition, infusion of BCAA-enriched solution may have a specific protein-sparing effect by increasing the protein synthesis rate even with liver damage. Hence, it is conceivable that infusion of BCAA improves protein metabolism in AHF.

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)

Overnight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis

Short-term (3 to 4 hours) infusion of branched-chain amino acids (BCAA) has been shown to suppress muscle protein breakdown. Whether these effects are sustained with chronic elevations of BCAA is not known. In the present study, we examined the effect of an overnight (16-hour) systemic BCAA infusion on whole-body and skeletal muscle amino acid metabolism, as assessed by simultaneously measured 3H-phenylalanine and 14C-leucine kinetics in eight normal volunteers; 10 overnight-fasted subjects studied during a 4-hour saline infusion served as controls. Overnight BCAA infusion increased plasma BCAA concentrations by fivefold to eightfold, and this was associated with a 20% to 60% decline in arterial concentrations of other amino acids. For Phe, this decline was mediated by a reduction in the systemic rate of appearance ([R a] 0.38 ± 0.03 v 0.60 ± 0.01 μmol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu R a, calculated more indirectly as the difference between the total Leu R a and the unlabeled Leu infusion rate, did not differ between groups. In the forearm, overnight BCAA infusion resulted in a diminished net release of Phe (−3 ± 2 v −18 ± 4 [saline] nmol/min/100 mL, P < .02), and BCAA balance became markedly positive (751 ± 93 v −75 ± 30, P < .001). The diminished net forearm Phe release was accounted for by a decrease in local Phe R a ( P < .02). As with the systemic endogenous Leu R a, forearm Leu R a was not reproducibly affected by infused BCAA. These findings suggest a need for caution in the application of amino acid tracer kinetic methods when tracer and unlabeled tracee are infused simultaneously. In conclusion, overnight BCAA infusion caused a sustained decline in most plasma amino acids and in net forearm release of Phe, effects attributable to a sustained suppression of whole-body and muscle proteolysis.

Cyclosporine inhibits the renal response to L-arginine in human kidney transplant recipients.

To evaluate the association of cyclosporine (CsA)-related nephrotoxicity with nitric oxide (NO) and endothelin, the effects of L-arginine (LA) and branched-chain amino acid (BCAA) infusions on renal hemodynamics in 5 normal volunteers and 12 renal transplant recipients were assessed. In normal humans, LA, but not BCAA, reduced mean arterial pressure and renal vascular resistance while increasing RPF and urinary nitrate (NO3-) excretion. Group 1 included six transplant recipients not on CsA; Group 2 subjects (N = 6) were receiving CsA. In both groups, mean arterial pressure declined during the infusion of LA (116 +/- 4 to 109 +/- 4 mm Hg; P < 0.001) but not BCAA (116 +/- 3 to 115 +/- 3; P = not significant). In Group 1, LA increased RPF 33 +/- 13% (329 +/- 48 to 436 +/- 77 mL/min per 1.73 m2; P = 0.01) and GFR 37 +/- 16% (95 +/- 7 to 130 +/- 18 mL/min per 1.73 m2; P = 0.01); renal vascular resistance declined 27 +/- 6%. In Group 2, LA did not affect renal hemodynamics. No changes occurred with BCAA in either group. LA increased urinary NO3-excretion by 27 +/- 17% in Group 1 (P < 0.05), but only by 16 +/- 13% in Group 2 (P = not significant). Urinary endothelin excretion was higher in Group 2 subjects (10.1 +/- 1.3 versus 5.3 +/- 0.8 pg/mL of GFR, P < 0.01). LA-induced renal vasodilation is associated with the increased urinary excretion of NO3-.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of valine, leucine, isoleucine, and a balanced amino acid solution on the seizure threshold to picrotoxin in rats

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, sleeping pattern, and appetite have been reported. The mechanism by which BCAA exerts their effects on CNS remains unclear. An infusion of a BCAA solution (300 mg/kg) has previously been found to increase the seizure threshold in rats to the proconvulsant drug picrotoxin, an antagonist on the GABA-benzodiazepine receptor complex. In this study, each of the BCAAs given separately (valine, leucine, isoleucine; 300 mg/kg) ( n = 10) increased the mean latency time to onset of seizures vs. placebo as an indication of an increased seizure threshold. A balanced amino acid solution (Vamin-Glucose ®) had no effect on the seizure threshold. Thus, these CNS effects are specific for BCAAs and occur with all three.

Administration of a branched-chain amino acid preparation during hepatic failure: a study emphasizing ammonia metabolism.

We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.

Effect of infusing branched-chain amino acid during incremental exercise with reduced muscle glycogen content

The aim of this study was to investigate whether, when muscle glycogen is reduced, a pre-exercise infusion of branched-chain amino acids (BCAA) modifies exercise performance or the metabolic and respiratory responses to incremental exercise. Six moderately trained volunteers took part in the following protocol on two occasions. On day 1, at 9 a.m. in the postabsorptive state, they performed a graded incremental exercise (increases of 35 W every 4 min) to exhaustion (Ex-1). A meal of 1,000 kcal (4,200 kJ; 60% protein, 40% fat) was consumed at 12 p.m. No food was then allowed until the end of the experiment (20-21 h later). A 90-min period of exercise at alternating high and moderate intensities, designed to deplete muscle glycogen, was performed between 6 p.m. and 7.30 p.m. The morning after (day 2), the subjects randomly received either a mixed solution of BCAA (260 mg x kg-1 x h-1 for 70 min), or saline. They then repeated the graded incremental exercise to exhaustion (Ex-2). Metabolic and respiratory measurements suggested a muscle glycogen-depleted state had been achieved. No significant differences were observed in total work performed, maximal oxygen uptake or plasma ammonia, alanine, and blood pyruvate concentrations in the two treatments. After BCAA infusion, higher blood lactate concentrations were observed at maximal power output in comparison with those during saline [BCAA 4.97 (SEM 0.41) mmol x l-1, Saline 3.88 (SEM 0.47) mmol x l-1, P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of parenteral glutamine and branched-chain amino acids on total parenteral nutrition-induced atrophy of the gut.

We tested the hypothesis that the provision of glutamine and branched-chain amino acids would reverse the gut atrophy that accompanies parenteral nutrition. Three hundred seventy-five rats were randomized into 15 groups to receive either conventional parenteral nutrition, rat food, glutamine-enriched parenteral nutrition (0.5% to 2.5%), branched-chain amino acid-enriched parenteral nutrition (0.8% to 2.0%), or glutamine plus branched-chain amino acid-enriched parenteral nutrition (0.5%/0.4% to 1.25%/1/0%). When compared with effects of conventional parenteral nutrition, the infusion of either glutamine or branched-chain amino acids partially reversed, in a dose-dependent manner, atrophy of the small bowel as assessed by gut weight (p < .05), mucosal weight (p < .05), villous height (p < .05), crypt cell production rate (p < .05), and mucosal protein concentration (p < .05). There was no effect on the large bowel. These results suggest that the parenteral infusion of either glutamine or branched-chain amino acids partially reverses the small-bowel atrophy that is associated with the infusion of solutions of conventional parenteral nutrients.

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.

Reduced thermogenic response to branched-chain amino acid infusion in healthy volunteers

Reduced thermogenic response to branched-chain amino acid infusion in healthy volunteers

Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.

The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.