Branched-chain Amino Acids In Patients Research Articles

Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection.

Branched chain amino acids (BCAA) supplementation may reduce the incidence of liver failure and hepatocellular carcinoma in patients with cirrhosis. We aimed to determine whether long-term dietary intake of BCAA is associated with liver-related mortality in a well-characterized cohort of North American patients with advanced fibrosis or compensated cirrhosis. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. The analysis included 656 patients who completed two Food Frequency Questionnaires. The primary exposure was BCAA intake measured in grams (g) per 1000 kilocalories (kcal) of energy intake (range 3.0-34.8 g/1000 kcal). During a median follow-up of 5.0 years, the incidence of liver-related death or transplantation was not significantly different among the four quartiles of BCAA intake before and after adjustment of confounders (AHR 1.02, 95% CI 0.81-1.27, P-value for trend = 0.89). There remains no association when BCAA was modeled as a ratio of BCAA to total protein intake or as absolute BCAA intake. Finally, BCAA intake was not associated with the risk of hepatocellular carcinoma, encephalopathy or clinical hepatic decompensation. We concluded that dietary BCAA intake was not associated with liver-related outcomes in HCV-infected patients with advanced fibrosis or compensated cirrhosis. The precise effect of BCAA in patients with liver disease warrants further study.

Branched-chain amino acids supplementation has beneficial effects on the progression of liver cirrhosis: A meta-analysis.

Liver cirrhosis (LC) is currently the 11th most common cause of death and 15th cause of morbidity globally. The treatment of LC is mainly aimed at etiological intervention, lifestyle intervention, prevention and treatment of complications and nutritional treatment. Nutritional treatment of LC mainly includes increasing dietary intake, food intake time and branched-chain amino acids (BCAAs). Despite the recommendation of BCAAs in some guidelines, adverse effects have been reported in studies so the efficacy and safety of BCAAs remain controversial. Currently, BCAAs have been widely used in chronic liver disease, while the summary of the effect of BCAAs on long-term prognosis is rare. To determine the effects of BCAAs in patients with LC. The PubMed, Cochrane Library, Embase and Web of Science databases were searched. The retrieval deadline was 1 October 2021 and there were no language restrictions set in the retrieval. The study was performed in strict accordance with the inclusion and exclusion criteria. Nine studies were finally included. The primary outcome was complications of LC. The secondary outcomes were nutritional status and liver function. This meta-analysis used the Review Manager, version 5 statistical package (Cochrane Collaboration, Oxford, England) for analysis. The analysis included nine studies that consisted of 1080 patients (554 in the BCAA groups and 526 in the control groups). The nine studies were randomized control trials (RCTs). The quality of the studies was assessed using the risk of bias method recommended by the Cochrane Collaboration. BCAAs reduced the rate of complications in LC patients [Risk ratio: 0.70, 95% confidence interval (CI): 0.56-0.88, P = 0.002] and improved patients' albumin levels [std mean difference SMD: 0.26, 95%CI: 0.12-0.40, P = 0.0002]. Meanwhile, BCAAs significantly ameliorated the levels of alanine transaminase (SMD: -2.03, 95%CI: -2.52 to -1.53, P < 0.00001) and aspartate aminotransferase (SMD: -1.8, 95%CI: -2.14 to -1.46, P < 0.00001). Meanwhile, glucose in the LC was significantly increased in BCAA-treated patients (MD: 13.04, 95%CI: 6.81-19.89, P = 0.0002). BCAAs reduce the incidence of complications in patients with LC and ameliorate nutritional status.

Levels of Acylcarnitines and Branched-Chain Amino Acids in Antipsychotic-Treated Patients with Paranoid Schizophrenia with Metabolic Syndrome.

Several studies have shown that patients with schizophrenia are at high risk for metabolic syndrome (MetS) and bioenergetic dysfunction. Because acylcarnitines are involved in bioenergetic pathways and reflect the functioning of mitochondria, we hypothesized that these compounds are biomarkers of MetS in schizophrenia. The aim of this work was to quantify acylcarnitines and branched-chain amino acids in patients with schizophrenia comorbid with MetS. The study included 112 patients with paranoid schizophrenia treated with antipsychotics. Among them, 39 subjects met criteria of MetS. Concentrations of 30 acylcarnitines and three amino acids in dry serum spots were measured by liquid chromatography coupled with tandem mass spectrometry. MetS patients were found to have higher levels of valeryl carnitine (C5), leucine/isoleucine, and alanine as compared with patients without MetS, indicating possible participation of these compounds in the pathogenesis of metabolic disorders in schizophrenia. In patients with paranoid schizophrenia with or without MetS, lower levels of carnitines C10, C10:1, C12, and C18 were recorded as compared with the healthy individuals (n = 70), implying deterioration of energy metabolism. We believe that this finding can be explained by effects of antipsychotic medication on an enzyme called carnitine-palmitoyl transferase I.

Plasma Changes of Branched-Chain Amino Acid in Patients with Esophageal Cancer.

BACKGROUNDStudies have indicated that branched amino acids play a crucial role in gene expression, protein metabolism, apoptosis, and restoration of hepatocytes and insulin resistance. This study aimed to compare the plasma levels of branched-chain amino acids in patients with esophageal cancer and normal individuals. METHODS Plasma levels of leucine and isoleucine of 37 patients with esophageal cancer and 37 healthy adults were investigated by high-pressure liquid chromatography. Data analysis was performed using SPSS (version 16) software, and t test was used to compare the plasma levels of branched-chain amino acids in the two groups. RESULTS In the patients group, the mean age ± SD was 63 ± 13.64 years, and 21 (56.8%) individuals were male. In the control group, the mean age ± SD was 64.24 ± 13.08 years, and 21 (54.1%) individuals were male. Plasma levels of leucine (37.68 ± 105) and isoleucine (22.43 ± 59.1) in patients with esophageal cancer were significantly reduced (p value of isoleucine:0.007, and leucine: 0.0001). CONCLUSION In the present study, the plasma levels of branched-chain amino acids in patients with esophageal cancer had changed. Evidence suggests that branched-chain amino acids are essential nutrients for cancer growth and are used by tumors in various biosynthetic pathways as energy sources. Thus, studies in this field can be useful in providing appropriate therapeutic approaches.

Cross-correlation of plasma concentrations of branched-chain amino acids: A comparison between healthy participants and patients with chronic kidney disease.

Plasma concentrations of branched-chain amino acids (BCAAs) are known to exhibit strong intercorrelations; however, the associated regulatory mechanism is not sufficiently understood. Furthermore, the mechanisms underlying the intercorrelation changes in metabolic disorders with the disease are unclear. Therefore, plasma BCAAs in patients with chronic kidney disease (CKD) were examined. This study included a healthy group of older participants (Group C; n=87, 46 males, 41 females) who had undergone health examinations at Sanyudo Hospital and a group of CKD patients (Group CKD; n=71, 49 males, 22 females) receiving maintenance hemodialysis at the same hospital. Samples from Group C were collected 12h after fasting. CKD samples were collected before and after hemodialysis (pre-HD and post-HD, respectively), without 12h fasting. The samples were analyzed for 38amino acids by SRL Inc., using liquid chromatography-mass spectrometry (LC-MS). Differences between the plasma BCAA concentrations of Group C and pre-HD were determined. Dialysis-induced BCAA losses were different for each BCAA. However, strong intercorrelations between the plasma concentrations of each BCAA were maintained. In addition, the regression lines did not converge at the origin and were in different positions for groups C, pre-HD, and post-HD. A different distribution of the constant (b) for each group was observed for each BCAA correlation when a in the regression line (Y=aX+b) was fixed at the value for Group C, and b was calculated. Strong intercorrelations among plasma concentrations of BCAAs were maintained in CKD patients both pre- and post-dialysis, whereas the changes in the plasma concentrations of each BCAA were different. We speculate that there is a novel mechanism that selectively regulates each BCAA and suggest that changes in the constant of the regression formula for correlation may have a novel function as an index for renal contribution to BCAA metabolism.

Intravenous and Oral Hyperammonemia Management

Hyperammonemia have significant morbidity and mortality. In this paper, we reviewed the latest research and evidence of both conventional and upcoming oral or intravenous treatments. New updates on the role of oral agents such as rifaximin, PEG, probiotics, glycerol phenylbutyrate, and zinc supplements in the management of both chronic hyperammonemia and overt hepatic encephalopathy have been discussed in this review. We discussed the recent findings on the role of branched-chain amino acids in patients with cirrhosis. Rifaximin role has expanded as mono or combination therapy in patients with hepatic encephalopathy. Probiotics and zinc might play a role in the prevention of overt hepatic encephalopathy. Newer oral agents such as activated carbon seem to be promising. Saline or albumin might play a role in diuretic-induced hyperammonemia but their role is yet to be determined. More research is needed for new interventions and treatment validation.

Taste Impairment and Compliance Improvement of Branched-Chain Amino Acids in Patients with Liver Cirrhosis

Background: Branched-chain amino acids (BCAA) are nutrients with a bitter taste, which causes low compliance in patients who need BCAA supplementation. Moreover, chronic liver disease is frequently complicated by taste impairment. The present study was designed to improve patient noncompliance regarding nutrients in liver disease. Methods: A taste questionnaire was administered to healthy controls, chronic hepatitis patients, and cirrhotic patients. Eleven different flavored powders that can be added to BCAA nutrients to reduce their unpleasant taste and smell were evaluated and categorized into three groups: delicious, fair and not good to drink. Patient serum zinc levels were measured and analyzed regarding their relationship to taste dysfunction. Results: Twenty-two healthy controls, 11 chronic hepatitis patients, and 36 liver cirrhosis patients were enrolled. Of the study subjects, 81.8% of healthy controls, 72.7% of chronic hepatitis patients and 50% of liver cirrhosis patients reported that a usual meal was delicious. The fruit-derived flavor and the yogurt flavor were well liked among each group. The mean serum zinc value of liver cirrhosis patients (53.7 g/dl) was significantly lower than that of chronic hepatitis patients (69.6 g/dl, P < 0.01). Conclusions: Half of the cirrhotic patients were dissatisfied with the taste of the usual meal. Zinc deficiency could be one cause of taste dysfunction and poor appetite in chronic liver disease. Flavors derived from fruits, which provide acidity and sweetness to counteract the taste of the BCAA nutrients, could improve palatability of BCAA supplementation for patients with liver disease.

Intraoperative infusion of branched-chain amino acids in patients undergoing gastrointestinal tumor surgery.

BackgroundThe purpose of this study is to investigate the effects of intraoperative infusion of branched-chain amino acids (BCAA) in patients undergoing gastrointestinal tumor surgery.MethodsSixty-one patients with gastrointestinal tumors undergoing gastrointestinal surgery were enrolled and randomly assigned to receive an intraoperative infusion of 3-compound BCAA solution (N = 20), amino acids (AA) solution (N = 21), or normal saline (NS) (N = 20). Nasopharyngeal temperature, blood glucose (BG), plasma insulin, and blood free fatty acids (FFA) concentrations were measured at 30 min before and 10 min after induction (T0,T1), 30 min and 2 h after skin incision (T2,T3), and 1 h after tracheal extubation (T4). Intensity of shivering and pain was accessed at 1 h after extubation.ResultsThe temperature in the BCAA and AA group was significantly higher than that in the NS group at T4 (P = 0.014 and 0.033). The incidence of shivering in the BCAA and AA group was significantly lower than in the NS group (P = 0.027 and 0.012). BG increased in AA group at T3 and T4 (P = 0.001 and 0.045). The plasma insulin concentration increased in the BCAA and AA group from T1 to T3. The plasma FFA concentrations in the BCAA group were lower than in the AA and NS group from T2 to T4.ConclusionsIntraoperative BCAA and AA infusion alleviated postoperative hypothermia and shivering. BCAA infusion also inhibited fat mobilization, without adversely affecting blood glucose.Trial registrationChiCTR-TRC-14004668Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-015-0751-y) contains supplementary material, which is available to authorized users.

Progress in application of branched-chain amino acids in patients with liver cirrhosis

Progress in application of branched-chain amino acids in patients with liver cirrhosis

Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy.

The aim of this retrospective cohort study was to clarify the effect of a branched-chain amino acids (BCAA) on the liver function and the prognosis of Child-Pugh class (C-P) A and B liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) undergoing hepatic arterial infusion chemotherapy (HAIC). Ninety-two adult Japanese patients with LC and aHCC underwent HAIC. They were in C-P A or B, and they showed multiple partial responses or stable disease. We excluded 11 patients classified as C-P C and 47 patients who showed no response. The patients were divided into an HAIC group receiving HAIC alone (n = 43) and a BCAA group treated with HAIC plus BCAA (n = 49). HAIC was delivered via the proper hepatic artery. The BCAA group also received oral administration of BCAA. In the BCAA group, serum albumin increased significantly after HAIC, while there were no significant changes in serum total bilirubin, serum aminotransferases, prothrombin time, ascites, and hepatic encephalopathy. The C-P score decreased significantly after HAIC compared with before HAIC in C-P B patients, although there was no significant change in C-P A patients. Survival of the BCAA group was significantly longer than that of the HAIC group, with the median survival time being 426 versus 272 days for C-P B patients, although there was no significant difference for C-P A patients. Branched-chain amino acids might improve the survival and C-P score by increasing serum albumin in C-P B patients with aHCC receiving HAIC.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.

Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma

To investigate the usefulness of branched-chain amino acids (BCAA) before transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). We investigated the usefulness of pre-intervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment. A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study. Mean changes from baseline (Δ) in serum albumin (Alb), C-reactive protein (CRP), and transaminase levels, as well as peak body temperature were also determined and compared at days 2, 5, and 10 after the start of TACE or RFA. In patients who underwent TACE or RFA, BCAA pre-intervention significantly suppressed the development of post- intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course. After TACE, the ΔAlb peaked on day 2, remained constantly lower in BCAA-treated patients, compared to the control group, and was -0.13 ± 0.42 g/dL in BCAA-treated patients and -0.33 ± 0.51 g/dL in untreated patients on day 10. The ΔCRP was also significantly lower in BCAA-treated patients on days 2, 5 and 10 after TACE. Like the trends noted after TACE, a similar tendency was noted as to the ΔAlb and ΔCRP after RFA. The changes in serum Alb level were inversely correlated with CRP changes; therefore, a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level. Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate post-operative complications in patients undergoing TACE or RFA.

Losses to Follow-Up Limit Conclusions Regarding the Efficacy of Branched-Chain Amino Acids in Patients With Hepatic Encephalopathy

1Leeds Gastroenterology Institute, Leeds General Infirmary, Leeds, UK 2Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK Correspondence: Alexander C. Ford, MBChB, MRCP, MD, Leeds Gastroenterology Institute, D Floor, Clarendon Wing, Leeds General Infirmary, Leeds LS1 3EX, UK. E-mail: [email protected] This letter to the editor underwent an editorial review.

The Benefit of the Supplementation of Perioperative Branched-Chain Amino Acids in Patients with Surgical Management for Hepatocellular Carcinoma: a Preliminary Study

The aim of this work was to study the benefit of supplementation with a branched chain amino acids enriched nutrient mixture on the physical and mental condition following hepatic surgery in patients with hepatocellular carcinoma (HCC). A total of 41 patients with HCC who underwent hepatic surgery (36 hepatic resection and five radiofrequency ablation therapy) were enrolled in this comparative study. These patients were divided into two groups: 13 patients received perioperative supplementation of a branched chain amino acids enriched nutrient mixture (AEN group) and 28 patients did not (control group). Between these two groups, laboratory data, postoperative complications and the length of hospital stay were analyzed comparatively. Restoration of peripheral lymphocyte count and serum total cholesterol level at 3 months after the operation was significantly faster in the AEN group than in the control group (P < 0.05). The length of hospitalization in the AEN group was significantly shorter than in the control group (P < 0.05). This preliminary case control study suggested that the perioperative supplementation of a branched chain amino acids enriched nutrient mixture is of clinical benefit for nutritional support of patients surgically managed for HCC in chronic liver disease.

Improvement of regional cerebral blood flow after oral intake of branched-chain amino acids in patients with cirrhosis

To evaluate the effect of oral intake of branched-chain amino acids (BCAA) on brain perfusion in patients with liver cirrhosis. Single photon emission computed tomography scans were performed in 43 patients with cirrhosis and in 15 age-matched healthy subjects. Twenty-nine out of forty-three patients were randomly treated with either BCAA granules or placebo, and single photon emission computed tomography was performed before and after the treatment. We measured the regional cerebral blood flow values using a three-dimensional stereotaxic region of interest template. Cirrhotic patients had regions of significant hypoperfusion in the bilateral central (right P=0.039, P<0.05; left P=0.006 P<0.01), parietal (right P=0.018, P<0.05; left P=0.009, P<0.01), angular (right P=0.039, P<0.05; left P 0.008, P<0.01), and left pericallosal segments (P=0.038 P<0.05) as compared with healthy subjects. A significant increase in cerebral perfusion was observed 70 min after the oral intake of BCAA in the angular (right P=0.012, P<0.05; left P=0.049, P<0.05), temporal (right P=0.012, P<0.05; left P=0.038, P<0.05), pericallosal segments (right P=0.025, P<0.05; left P=0.049, P<0.05) and left precentral (P=0.044, P<0.05), parietal (P=0.040, P<0.05) and thalamus (P=0.033, P<0.05). No significant change in perfusion was observed in the placebo group. Administration of BCAA rapidly improves cerebral perfusion.

Infusion of dipeptides as nutritional substrates for glutamine, tyrosine, and branched-chain amino acids in patients with acute pancreatitis

In this study we investigated the effect of a total parenteral nutrition supplemented with synthetic dipeptides on plasma and muscle amino acid metabolism in four patients with acute pancreatitis. We infused an amino acid solution containing alanylglutamine, glycylglutamine, glycylvaline, glycylisoleucine, glylcylleucine, and glycyltyrosine for a period of five days in daily dosages of 10.3, 22.1, 68.8, 37.2, 42.5, and 15.7 mmol, respectively. The plasma levels remained below 100 μmol/L for all infused dipeptides. The plasma concentrations of alanylglutamine were not measurable. Mean peptide urine excretion remained below 5%, with the exception of glycylglutamine (8.5% ± 5.1%). Arteriovenous concentration differences of the dipeptides across the leg were not significantly different from zero, indicating that the infused dipeptides have no important role in the nitrogen exchange of skeletal muscle. A marked intracellular glutamine deficiency in skeletal muscle was found in all four patients (5.1 ± 0.6 mmol/L v 19.5 ± 0.8 in healthy subjects) before infusion. Intracellular glutamine concentration was significantly higher after the infusion period (5.1 ± 0.7 v 9.5 ± 1.8 mmol/L, P > .05), but no normalization of the intracellular glutamine levels was achieved by the infusion of the two glutamine-containing peptides. We conclude that peptides are well metabolized as substrates for parenteral nutrition in catabolic patients. Furthermore, the infusion of glutamine peptides caused a significant increase of intracellular glutamine levels; however, the dosage of glutamine peptides was too low to normalize the muscular glutamine concentrations.

Inhibition of branched-chain amino acid degradation by ketone bodies

The present study deals with mechanisms for the accumulation of intermediates in the catabolism of branched-chain amino acids in patients with ketoacidosis. Two different systems have been developed to measure the degradation rates of leucine and valine intermediates in rat liver mitochondria. 3-Hydroxybutyrate was found to inhibit the conversion of isobutyryl-CoA to propionyl-CoA, and this appeared to be partly due to an elevated NADH2/NAD ratio. 3-Methylcrotonyl-CoA carboxylase was strongly inhibited by acetoacetyl-CoA and to a lesser extent by the nonesterified ketone bodies. These inhibitory effects of ketone bodies may explain the accumulation of branched-chain amino acid intermediates during ketoacidosis.