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PubMed2006

Branched-chain amino acid enriched supplements as therapy for liver disease.

Altered amino acid metabolism is a hallmark of liver disease, characterized by low levels of circulating BCAAs and elevated levels of circulating aromatic amino acids, and methionine. Although overwhelming evidence indicates that the incidence of complications of liver disease increases with malnutrition, the reported impact of nutritional therapy, specifically BCAA supplementation, on outcomes in patients with liver disease has varied with the indication. Multiple small studies report the beneficial effects of BCAA supplementation, including improved metabolic profiles, as measured by protein sparing and/or normalization of respiratory quotients and clinical improvement of hepatic encephalopathy. Other studies have failed to show a clinical benefit of BCAA supplementation. The data concerning the impact of BCAA supplementation in prophylaxis of long-term morbidity and mortality in patients with cirrhosis is more promising and has been the subject of 2, large randomized controlled trials. In a study of 174 patients with advanced cirrhosis, who were randomized to either BCAA or 1 of 2 control arms, the combined event rates were seen to be significantly reduced in the BCAA supplementation arm, although this was not true for individual complications. In a more recent, larger, randomized controlled trial (n = 646) using a more palatable formulation, investigators demonstrated that long-term BCAA supplementation is associated with decreased frequency of hepatic failure and overall complication frequency. Both studies found improved nutritional status associated with BCAA supplementation. On balance, BCAA supplementation appears to be associated with decreased frequency of complications of cirrhosis and improved nutritional status when prescribed as maintenance therapy. Cost and palatability may limit the potential applicability of this treatment modality.

Amino Acids, Branched-Chain↗

PubMed2001

Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis.

BACKGROUND: Anorexia may be associated with decreased plasma levels of branched-chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients, oral BCAA supplementation may improve anorexia, resulting in improved nutritional status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28 patients with low plasma albumin concentration (<3.5 g/dl) were classified as the malnourished group; they also suffered from anorexia. The other 16 patients did not complain of anorexia and were classified as the well-nourished group. We performed a 12-month, placebo-controlled, double-blind study on the malnourished group. Fourteen patients each received daily oral BCAA supplementation (12 g/day) or a placebo in random order in a crossover trial for 6 months. Body fat percentage, lean body mass, plasma albumin concentration, dietary protein and caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group. In BCAA-treated malnourished patients, anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients. After 6 months of BCAA supplementation, anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake decreased, but the favourable nutritional status persisted for the next 6 months. In 14 patients initially treated with a placebo, no significant changes in nutritional parameters were observed during the first 6 months. However, positive results were obtained by BCAA supplementation during the subsequent 6 months, and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl. CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients.

Administration, Oral↗

PubMed1990

Relationship of plasma cholesterol level to doses of branch-chain amino acids in sepsis.

Plasma cholesterol levels, plasma lactate, and total body RQ were measured in septic patients undergoing total parenteral nutrition (TPN) with glucose, fat, and two different branch-chain amino acid admixtures (49% BCAA and 16% BCAA). Mean plasma cholesterol for all measurements (2.61 +/- 0.94 [SD] mmol/L) was lower than normal; however, it was higher with 49% BCAA than with 16% BCAA (2.94 +/- 0.95 vs. 2.27 +/- 0.81 mmol/L, p less than .001) for comparable loads of glucose, fat, and total amino acids. Plasma lactate and RQ were lower with 49% BCAA than with 16% BCAA (p less than .001 for both). Cholesterol was directly related to the absolute dose of BCAA (p less than .001), was unrelated to the dose of non-BCAA, and was inversely related to lactate (p less than .001). These results suggest that BCAA ketoacids contribute to cholesterol synthesis in sepsis, as well as being an oxidative source. The data also suggest that the reduction in alanine in BCAA-enriched amino-acid TPN assists in the lowering of plasma lactate secondary to abnormal septic glucose metabolism.

Adult↗

PubMed1986

Effect of a diet rich in branched chain amino acids on severely burned guinea pigs.

This study was performed to investigate the effects of dietary supplementation with branched-chain amino acids (BCAA) for postburn nutritional management. Seventy-one burned guinea pigs (30% TBSA) with previously placed catheter gastrostomies were divided into six groups. The first, second, and third groups received 10%, 20%, and 30%, respectively, of total calories as whey protein. The other three groups received BCAA supplementation to increase BCAA to 50% of total amino acids, compared to 21.5% BCAA content in whey protein. Groups I and IV received isonitrogenous intake, as did groups II and V, and III and VI, respectively. After an initial 3-day adaptation period, all animals in all groups received continuous isocaloric (175 kcal/kg/day) intragastric tube feeding until postburn day (PBD) 14. At PBD 14, although BCAA-supplemented groups showed very high plasma levels of BCAA (IV: 169%; V: 306%; VI: 770% of normal), no BCAA group showed evidence of any beneficial effect in various nutritional parameters when compared with the corresponding whey protein group with isonitrogenous intake. Cumulative nitrogen balance and mortality during 14 days were significantly worse in BCAA groups IV and VI than in control groups I and III, respectively. It is concluded that BCAA supplementation to enteral diets has no beneficial effect for postburn nutritional management following severe burn injury. It is further suggested that when nitrogen intake is too low or very high, BCAA supplementation may have an adverse effect.

Amino Acids, Branched-Chain↗

PubMed1997

Pre-exercise branched-chain amino acid administration increases endurance performance in rats.

This study investigated the effects of pre-exercise branched-chain amino acid (BCAA) administration on blood ammonia levels and on time to exhaustion during treadmill exercise in rats. Adult female Wistar rats were trained on a motor driven treadmill. After a 24-h fast, rats were injected intraperitoneally (i.p.) with 1 mL of placebo or BCAA (30 mg), 5 min before performing 30 min of submaximal exercise (N = 18) or running to exhaustion (N = 12). In both cases, rats were sacrificed immediately following exercise, and blood was collected for the measurement of glucose, nonesterified fatty acid (NEFA), lactic acid, BCAA, ammonia, and free-tryptophan (free-TRP) levels. Control values were obtained from sedentary rats that were subjected to identical treatments and procedures (N = 30). Plasma BCAA levels increased threefold within 5 min after BCAA administration. Mean run time to exhaustion was significantly longer (P < 0.01) after BCAA administration (99 +/- 9 min) compared with placebo (76 +/- 4 min). During exercise, blood ammonia levels were significantly higher (P < 0.01) in the BCAA treated compared with those in the placebo treated rats both in the 30-min exercise bout (113 +/- 25 mumol.L-1 (BCAA) vs 89 +/- 16 mumol.L-1) and following exercise to exhaustion (186 +/- 44 mumol.L-1 (BCAA) vs 123 +/- 19 mumol.L-1). These data demonstrate that BCAA administration in rats results in enhanced endurance performance and an increase in blood ammonia during exercise.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

The optimal branched-chain to total amino acid ratio in the injury-adapted amino acid formulation.

Several recent studies have suggested that solutions containing increased amounts of branched-chain amino acids (BCAA) might be useful in the treatment of patients with trauma and/or sepsis. In this study we investigated the optimal amount of BCAA in a balanced nutritional solution in an injured rat laparotomy model. The amino acid content of a standard BCAA-enriched amino acid solution was enriched to 40, 45, and 50% by the addition of equimolar amounts of the three BCAA. Rats were infused with either 3.6 cal/100 g body weight/24 hr or with 18 cal/100 g body weight/24 hr with either a 40, 45, or 50% BCAA mixture and evaluated for nitrogen balance, plasma amino acid levels, and levels of plasma blood urea nitrogen, creatinine, glucose, albumin, and blood ammonia. Nitrogen balance was negative in rats receiving only 3.6 cal/100 g body weight/24 hr, but was least negative in the group receiving 45% BCAA. Nitrogen balance was positive in groups receiving 18 cal/100 g body weight/24 hr, but was most positive in groups receiving 40 or 45% BCAA-containing solutions. Plasma amino acid patterns were least distorted in the 40 and 45% formulations. Blood ammonia was highest in the 40% BCAA group and plasma albumin was best maintained in the 45% BCAA group regardless of the amount of caloric supply. The results suggest that a 45% BCAA-enriched solution is the most appropriate in this injured rat model.

Amino Acids↗

PubMedDate not supplied

Branched-chain amino acids metabolic support in surgical patients: a randomized, controlled trial in patients with subtotal or total gastrectomy in 16 Japanese institutions.

A prospective, randomized, controlled trial of nutritional effects of branched-chain-enriched amino acid (BCAA) solution was undertaken in 173 surgical patients with gastric cancer. Eighty-six and 87 patients underwent subtotal and total gastrectomy, respectively. The effects were evaluated in total parenteral nutrition (TPN) in an isocaloric/isonitrogenous setting where the major difference between the group was the amount of BCAA received. Each 80 patients in the control and the BCAA groups completed the trial. The group receiving BCAA-enriched amino acid solution demonstrated a statistically significant improvement on days 2 and 3 in nitrogen balance in patients with total gastrectomy. Three-methyl-histidine excretion gradually decreased after day 1, and the values on day 7 were significantly lower than those on day 1 in the BCAA group in both those receiving subtotal and total gastrectomy. There were no significant differences of serum albumin and rapid turnover proteins between the control and BCAA groups in both those receiving subtotal and total gastrectomy. Plasma BCAA level and BCAA to aromatic amino acid (AAA) ratio were significantly higher, and AAA level was significantly lower in the BCAA group than in the control group. There were no serious complications encountered during the observation period in both groups. These results indicated that a BCAA-enriched amino acid solution can improve metabolism and maintains good nitrogen retention without increasing side effects as compared with a conventional amino acid solution for nutritional support of patients who have received subtotal or total gastrectomy.

Adolescent↗

PubMed2006

Effect of orthotopic liver transplantation (OLT) on branched-chain amino acid requirement.

Little is known regarding the impact of liver transplantation on amino acid requirements in children. Since plasma levels of the branched-chain amino acids (BCAA) are decreased in the presence of normal levels of the aromatic amino acids after liver transplantation, normalization of hepatic function may not fully correct changes in BCAA metabolism that occur in the pretransplant period. The goal of the present study was to determine total BCAA requirements of children following liver transplantation. The requirement of total BCAA was determined using indicator amino acid oxidation (IAAO) in five clinically stable children (5.7 +/- 3.5 y, mean +/- SD) 1-8 y post liver transplantation. Children received in random order 6 graded intakes of total BCAA. Individual BCAA in the test diet were provided in the same proportions as present in egg protein to minimize the potential interactive effects of individual BCAA on assessment of requirement. Total BCAA requirement was determined by measuring the oxidation of L-[1-13C] phenylalanine to 13CO2 [F13CO2 in micromol/kg/h], after a primed, continuous infusion of the tracer and using a two-phase linear regression crossover regression analysis. The estimated average requirement and the upper limit of the 95% CI for total BCAA in children who have undergone liver transplantation were 172 and 206 mg/kg/d), respectively. Total BCAA requirement in children who have undergone orthotopic liver transplantation (OLT) remain increased in the post-liver transplant period when compared with healthy school aged children, but is decreased when compared with children with mild-moderate chronic cholestatic (MCC) liver disease.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

Effect of acute and chronic branched-chain amino acids on energy metabolism and muscle performance.

The aim of this study was to report the effects of acute and chronic branched-chain amino acids (BCAA) administration on energy metabolism and muscle performance. In the acute study which was double-blind, cross-over and placebo-controlled, 12 healthy male volunteers were administered orally on two consecutive days either BCAA (14.4 g/day) or isocaloric placebo; this was followed by measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2) for 180 min by indirect calorimetry. In the chronic study, 10 healthy male volunteers were supplemented with BCAA (14.4 g/day) for 30 days. Before (T0) and after (T1) chronic BCAA administration, VO2, arm muscle area (AMA) and maximal voluntary contraction of forearm muscles (grip strength, GS) were evaluated. Acute study: Both meals increased mean respiratory quotient (RQ) from baseline: in the placebo group, this increase was short-term only (between 15 and 60 min), while this effect on RQ lasted for 120 min in the BCAA group. Moreover, between 30 and 90 min, mean RQ was significantly higher in the BCAA group than in the placebo group. Chronic study: GS increased significantly following chronic BCAA administration without significant changes in the AMA. At T0, VO2 increased significantly during the GS test, whereas at T1 no significant increase was observed. In conclusion, no excess thermogenesis could be detected as compared with placebo following acute BCAA administration, indirectly suggesting a relevant contribution of peripheral catabolic (bypassing liver) pathway to BCAA metabolism; furthermore, chronic BCAA supplementation improved the physical fitness of untrained healthy subjects, as demonstrated by the lack of 02 uptake increase during sustained hand grip test.

Administration, Oral↗

PubMed1991

[Experimental study on metabolism of branched chain amino acids after partial hepatectomy].

Metabolism of branched chain amino acids (BCAA) after partial hepatectomy was investigated. Total amino acids of the plasma in the rats undergone 70% partial hepatectomy increased significantly as compared with those of control animals. This increase was due to an increase of sum of all amino acids other than BCAA, whereas total amount of BCAA was unaffected. Both BCAA aminotransferase (BCAA-AT) and branched chain ketoacid dehydrogenase (BCKA-DH), the rate limiting enzymes in BCAA metabolism, increased in mitochondria of the liver and BCAA-AT increased in skeletal muscle homogenate. These increases of both enzymes might reduce the concentration of BCAA relatively. Mitochondrial respiration such as state 3 respiration, respiratory control index (RCI) and ATP synthesis in mitochondria of regenerating liver increased remarkably, when not only succinate but also alpha-ketoisocaproic acid was used as a substrate. ATP synthesis, however, was much higher and mitochondrial respiration was more coupled when alpha-ketoisocaproic acid was used as a substrate. These results suggest that BCAA metabolism was activated after partial hepatectomy and BCAA might serve as an appropriate substrate for regenerating liver.

Amino Acids, Branched-Chain↗

PubMed2024

Association between Branched-Chain amino acids and Epilepsy: A Mendelian randomized study.

BACKGROUND: Branched-chain amino acids (BCAAs) have been affected epilepsy, yet conclusions remain inconclusive, lacking causal evidence regarding whether BCAAs affect epilepsy. Systematic exploration of the causal relationship between BCAAs and epilepsy could hand out new ideas for the treatment of epilepsy. METHODS: Utilizing bidirectional Mendelian randomization (MR) study, we investigated the causal relationship between BCAA levels and epilepsy. BCAA levels from genome-wide association studies (GWAS), including total BCAAs, leucine levels, isoleucine levels, and valine levels, were employed. Causal relationships were explored applying the method of inverse variance-weighted (IVW) and MR-Egger, followed by sensitivity analyses of the results to evaluate heterogeneity and pleiotropy. RESULTS: Through strict genetic variant selection, we find some related SNPs, total BCAA levels (9), leucine levels (11), isoleucine levels (7), and valine levels (6) as instrumental variables for our MR analysis. Following IVW and sensitivity analysis, total BCAAs levels (OR = 1.14, 95 % CI = 1.019 ∼ 1.285, P = 0.022) and leucine levels (OR = 1.15, 95 % CI = 1.018 ∼ 1.304, P = 0.025) had significant correlation with epilepsy. CONCLUSIONS: There exists a causal relationship between the levels of total BCAAs and leucine with epilepsy, offering the new ideas into epilepsy potential mechanisms, holding significant implications for its prevention and treatment.

Humans↗

PubMed1986

Improved protein kinetics and albumin synthesis by branched chain amino acid-enriched total parenteral nutrition in cancer cachexia. A prospective randomized crossover trial.

A prospective randomized crossover trial was conducted to determine the effect of a branched chain amino acid (BCAA)-enriched solution on whole body leucine kinetics and fractional rates of albumin synthesis in patients with intra-abdominal metastatic adenocarcinoma. Ten malnourished cancer patients were provided isonitrogenous amounts of both a conventional total parenteral nutrition (TPN) formula containing 19% BCAA and a BCAA-enriched TPN formula containing 50% of the amino acids as BCAA in a random order. Whole body protein turnover was determined by a 10 hour continuous infusion of leucine 14C. Increased whole body leucine flux (68 +/- 5 mumols/kg BW/hr versus 145 +/- 11; mean +/- SEM; P less than 0.001) and oxidation (13 +/- 2 mumols/kg BW/hr to 46 +/- 5; P less than 0.001) were determined on the BCAA-enriched TPN. Increased whole body protein synthesis (2.2 +/- 0.2 g protein/kg BW/day versus 3.9 +/- 0.3; P less than 0.005) and leucine balance (2.5 +/- 0.4 g leucine/d versus 6.5 +/- 0.6; P less than 0.001) were also observed in patients receiving the BCAA-enriched TPN solution. Leucine release from protein breakdown was not statistically elevated (1.65 +/- 0.18 g protein/kg BW/d versus 2.48 +/- 0.40; P greater than 0.05) but, incorporation of leucine 14C into plasma albumin was significantly elevated (2.37 +/- 0.23 mumols/g/hr to 4.21 +/- 0.33; P less than 0.001) when the patients received BCAA-enriched TPN. Despite the better leucine balance, the improvement in the 24-hour urinary nitrogen balance was not statistically significant (6.6 +/- 3.9 g protein/d versus 11.4 +/- 2.9; control versus BCAA-enriched; P = 0.15). BCAA-enriched formulas improve whole body leucine kinetics, fractional rates of albumin synthesis, and leucine balance, and thus may favorably influence protein metabolism in cancer cachexia.

Abdominal Neoplasms↗

PubMed2003

Branched-chain amino acids for hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA for patients with hepatic encephalopathy. SEARCH STRATEGY: We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue 3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies. SELECTION CRITERIA: Randomised trials comparing BCAA with any kind of control therapy for hepatic encephalopathy were included, regardless of blinding, language, or publication status. DATA COLLECTION AND ANALYSIS: Trial inclusion and data extraction were made independently by two reviewers. Our primary outcome was improvement of hepatic encephalopathy. Statistical heterogeneity was tested using random effects and fixed effect models. Binary outcomes are reported as risk ratios (RR) based on a random effects model. MAIN RESULTS: Eleven randomised trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or isonitrogenous control were included. The median number of patients in each trial was 55 (range 22 to 75). Follow-up after treatment was reported in four trials (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA significantly increased the number of patients improving from hepatic encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that methodological quality had significant impact on the results. We found no evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to 1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to 1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73, three trials). REVIEWER'S CONCLUSIONS: We did not find convincing evidence that BCAA had a significant beneficial effect on patients with hepatic encephalopathy. The trials performed in this field were small with short follow-up and most had low methodological quality.

Amino Acids, Branched-Chain↗

PubMed1990

Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial.

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.

Amino Acids, Branched-Chain↗

PubMed1992

Branched-chain amino acid supplementation during trekking at high altitude. The effects on loss of body mass, body composition, and muscle power.

To investigate the influence of a branched-chain amino acid (BCAA) supplementation on chronic hypoxia-related loss of body mass and muscle loss, 16 subjects [age 35.8 (SD 5.6) years] participating in a 21-day trek at a mean altitude of 3,255 (SD 458) m, were divided in two age-, sex- and fitness-matched groups and took either a dietary supplementation of BCAA (5.76, 2.88 and 2.88 g per day of leucine, isoleucine and valine, respectively) or a placebo (PLAC) in a controlled double-blind manner. Daily energy intake at altitude decreased by 4% in both groups compared with sea level. After altitude exposure both groups showed a significant loss of body mass, 1.7% and 2.8% for BCAA and PLAC, respectively. Fat mass had decreased significantly by 11.7% for BCAA and 10.3% for PLAC, whereas BCAA showed a significantly increased lean mass of 1.5%, as opposed to no change in PLAC. Arm muscle cross-sectional area tended to increase in BCAA, whereas there was a significant decrease of 6.8% in PLAC (P < 0.05 between groups). The same tendency, although not significant, was observed for the thigh muscle cross-sectional area. On the whole it seemed that PLAC had been catabolizing whereas BCAA had been synthesizing muscle tissue. Single jump height from a squatted position showed a similar tendency to increase in both groups. Lower limb maximal power decreased less in BCAA than in PLAC (2.4% vs 7.8%, P < 0.05). We concluded that BCAA supplementation may prevent muscle loss during chronic hypobaric hypoxia.

Adult↗

PubMed2005

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making.

RATIONALE: We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function. OBJECTIVES: To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP. METHODS: We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion. RESULTS: Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses. CONCLUSIONS: A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.

Adult↗

PubMed1999

Branched chain amino acids decrease tardive dyskinesia symptoms.

RATIONALE: Prior studies had suggested (a) that a lessened ability to clear ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe), was associated with having tardive dyskinesia (TD), and (b) that greater availability of a group of LNAA, the branched chain amino acids (BCAA), concomitant with the lower availability of Phe to the brain are associated with a decrease in TD symptoms. The present study was then conducted to test whether increasing the daily intake of the BCAA would decrease the symptoms of TD. METHODS: A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. Plasma levels of the LNAA were also collected throughout the trial. RESULTS: A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%. BCAA administration increased plasma BCAA concentrations and BCAA/LNAA ratios and decreased plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a strong significant correlation between the percent increase in the plasma BCAA values at the first administration and the percent improvement in TD over the trial in eight of the nine subjects. CONCLUSIONS: The BCAA show promise as a treatment for TD. The decrease in TD symptoms seen in the trial may have been modulated by the BCAA treatment-induced increased availability of the BCAA and decreased availability of Phe to the brain.

Amino Acids, Branched-Chain↗

PubMed1995

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 ([Ra] 0.38 +/- 0.03 v 0.60 +/- 0.01 mumol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu Ra, calculated more indirectly as the difference between the total Leu Ra 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 Ra (P < .02). As with the systemic endogenous Leu Ra, forearm Leu Ra was not reproducibly affected by infused BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗