Long-Term Carbohydrate-Containing Late-Evening Snack Significantly Improves the Ratio of Branched Chain Amino Acids to Aromatic Amino Acids in Adults with Liver Cirrhosis due to Hepatitis B.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal.

BACKGROUND: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown. METHODS: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal. RESULTS: Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover. CONCLUSIONS: In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

Dietary supplementation with aromatic amino acids decreased triglycerides and alleviated hepatic steatosis by stimulating bile acid synthesis in mice.

Emerging evidence shows that amino acids can modulate lipid metabolism. Aromatic amino acids (AAAs) serve as important precursors of several neurotransmitters and metabolic regulators that play a vital role in regulating nutrient metabolism. But whether AAAs have a lipid-lowering function remains unknown. Here mice were fed amino acid-defined diets containing AAAs at 1.82% and 3.64% for 3 weeks. We demonstrated that double AAA intake significantly decreased the serum and hepatic triglycerides and serum low-density lipoprotein cholesterol, but increased the high-density lipoprotein cholesterol as well as insulin tolerance. Combined metabolomic and transcriptomic analysis showed that the hepatic acidic pathway of bile acid synthesis was responsible for the improvement in lipid metabolism by AAA treatment. This study suggests that AAAs have the potential to ameliorate steatosis and provides a new alternative to improve lipid metabolism.

Attenuation of Carbon Tetrachloride-Induced Hepatic Toxicity by a Dietary Supplement.

Advanced liver disease (ALD) is often characterized with overt malnutrition and liver fibrosis. In this study, a dietary supplement (DS) was first developed, including branch chain amino acids, fat soluble vitamins, zinc, medium chain triglycerides, soy lecithin, L-carnitine, and n-3 polyunsaturated fatty acids. Benefits of DS were then tested using an ALD rat model treated with carbon tetrachloride (CCl4) for 6, 8, and 10 weeks, respectively. Our study showed that CCl4-induced drop of serum albumin and ratio of branch chain to aromatic amino acids were significantly prevented at all three time points. DS also mitigated CCl4-induced elevation of classical liver function markers (alanine aminotransferase, aspartate aminotransferase, and bilirubin) at certain time points, depending on specific liver function markers. Moreover, CCl4-induced liver fibrosis was strongly inhibited at all three time points in a transforming growth factor beta (TGF-ß) independent manner. These findings indicated multi-faceted benefits of DS in this animal model, suggesting that it could be a useful adjunctive treatment of ALD in clinic.

Metabolic changes during a field experiment in a world-class windsurfing athlete: a trial with multivariate analyses.

Physical exercise affects hematological equilibrium and metabolism. This study evaluated the biochemical and hematological responses of a male world-class athlete in sailing who is ranked among the top athletes on the official ISAF ranking list of windsurfing, class RS:X. The results describe the metabolic adaptations of this athlete in response to exercise in two training situations: the first when the athlete was using the usual training and dietary protocol, and the second following training and nutritional interventions based on a careful analysis of his diet and metabolic changes measured in a simulated competition. The intervention protocol for this study consisted of a 3-month facility-based program using neuromuscular training (NT), aerobic training (AT), and nutritional changes to promote anabolism and correct micronutrient malnutrition. Nutritional and training intervention produced an increase in the plasma availability of branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), alanine, glutamate, and glutamine during exercise. Both training and nutritional interventions reduced ammonemia, uricemia, and uremia. In addition, we are able to correct a significant drop in potassium levels during races by correct supplementation. Due to the uniqueness of this experiment, these results may not apply to other windsurfers, but we nonetheless had the opportunity to characterize the metabolic adaptations of this athlete. We also proposed the importance of in-field metabolic analyses to the understanding, support, and training of world-class elite athletes.

Effects of branched-chain amino acid supplementation on plasma concentrations of free amino acids, insulin, and energy substrates in young men.

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.

Effects of squat exercise and branched-chain amino acid supplementation on plasma free amino acid concentrations in young women.

The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosis.

BACKGROUND AND AIM: Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. METHODS: Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. RESULTS: In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. CONCLUSIONS: The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation.

Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men.

OBJECTIVE: The efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men with psychiatric disorders was tested. METHOD: Public-sector psychiatric patients with long histories of antipsychotic treatment and presumably long-standing tardive dyskinesia were randomly assigned to receive branched-chain amino acids or placebo. Treatment frequency was three times a day, 7 days a week for 3 weeks. The efficacy measure was a frequency count of videotaped tardive dyskinesia movements. RESULTS: A robust and highly significant difference was observed between patients who received high-dose branched-chain amino acids (222 mg/kg of body weight t.i.d.) (N=18) and those who received placebo (N=18) in the percent change in tardive dyskinesia symptoms from baseline to the end of the 3-week trial. Significant and marked differences were seen between the two groups at the >/=30% and >/=60% levels of decrease in tardive dyskinesia symptoms. No clinically significant differences were seen between the pre- and posttrial results of physical examinations and laboratory screening tests. Minimal gastrointestinal symptoms occurred during the trial. The reduction in tardive dyskinesia symptoms in the amino acids group was not related to changes in antipsychotic and glucose plasma levels. A mechanism of response related to decreased amine neurotransmitter synthesis was suggested by the significant positive correlations observed between decreases in tardive dyskinesia symptoms and decreases in aromatic amino acid plasma concentrations over the course of the trial. CONCLUSIONS: Branched-chain amino acids constitute a novel, safe treatment for tardive dyskinesia, with a strong potential for providing significant improvement in the diseased physiognomy of the afflicted person.

Serial therapies oriented by surgery for large primary liver carcinoma.

OBJECTIVE: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of primary large liver cancers. METHODS: From January 1993 to June 1999, 191 patients with large liver carcinoma were treated surgically. The size of tumors varied from 5.2 to 19.7 cm (mean 9.4 cm). Several types of liver resections were made in 121 patients and as a supplement, cryosurgery was carried out for the remaining 70 patients. Importable drug delivery system was instituted intraoperatively. Transcatheter arterial chemo-embolization (THP 30-60 mg, E-ADM 20-40 mg, CDDP 40-80 mg, MMC 10-20 mg, iodin oil 5-30 ml), percutaneous ethanol injection, bioimmunotherapy and traditional Chinese medicine were used pre- and post-operatively. CT angiography and CT during arterial portography were used to find satellite nodules. Early stage recurrences were predicted by AFPmRNA in peripheral blood. Child-Pugh's classification plus branch chain amino acid/aromatic amino acid ratio (BCAA/AAA) was adopted in evaluating pre-operative liver functions. RESULTS: Marked results were observed after serial treatments oriented by surgery. The 1-, 3- and 5-year survival rates in resection group were 75.8%, 45.6% and 30.4%, respectively. The 1- and 3-year survival rates in cryosurgery group were 63.2% and 37.0%. The operative mortality was 1.57%. Recurrence rates were 69.2% in AFPmRNA positive group and 33.3% in AFPmRNA negative group (P<0.05). The BCAA/AAA ratio was lower than 1.5 in two patients who died of hepatic failure after resection. CONCLUSIONS: Serial treatments with surgery as the chief modality gives satisfactory results in patients with large primary liver carcinoma. This regimen should be regarded as a main strategy to deal with large liver carcinoma. AFPmRNA in the peripheral blood, signifying a recurrence, may become a new clinical parameter. The BCAA/AAA ratio plus Child-Pugh's classification is able to evaluate more accurately liver function reserve before surgery.