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.

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy.

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer's ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE.

Plasma concentrations of branched-chain amino acids differ with Holstein genetic strain in pasture-based dairy systems.

In pasture-based systems, there are nutritional and climatic challenges exacerbated across lactation; thus, dairy cows require an enhanced adaptive capacity compared with cows in confined systems. We aimed to evaluate the effect of lactation stage (21 vs. 180 days in milk, DIM) and Holstein genetic strain (North American Holstein, NAH, n = 8; New Zealand Holstein, NZH, n = 8) on metabolic adaptations of grazing dairy cows through plasma metabolomic profiling and its association with classical metabolites. Although 67 metabolites were affected (FDR < 0.05) by DIM, no metabolite was observed to differ between genetic strains while only alanine was affected (FDR = 0.02) by the interaction between genetic strain and DIM. However, complementary tools for time-series analysis (ASCA analysis, MEBA ranking) indicated that alanine and the branched-chain amino acids (BCAA) differed between genetic strains in a lactation-stage dependent manner. Indeed, NZH cows had lower (P-Tukey < 0.05) plasma concentrations of leucine, isoleucine and valine than NAH cows at 21 DIM, probably signaling for greater insulin sensitivity. Metabolic pathway analysis also revealed that, independently of genetic strains, AA metabolism might be structurally involved in homeorhetic changes as 40% (19/46) of metabolic pathways differentially expressed (FDR < 0.05) between 21 and 180 DIM belonged to AA metabolism.

The probiotic effects of AB23A on high-fat-diet-induced non-alcoholic fatty liver disease in mice may be associated with suppressing the serum levels of lipopolysaccharides and branched-chain amino acids.

Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from Rhizoma alisamatis that has been widely used as a traditional Chinese medicine (TCM). Previous studies have documented the beneficial effect of AB23A on non-alcoholic fatty liver disease (NAFLD), but the functional interactions between gut microbiota and the anti-NAFLD effect of AB23A remain unclear. In this study, we investigated the benefits of experimental treatment with AB23A on gut microbiota dysbiosis in NAFLD with an obesity model. C57BL/6J mice were administrated a high-fat diet (HFD) with or without AB23A for 12 weeks. AB23A significantly improved metabolic phenotype in the HFD-fed mice. Moreover, results of 16S rRNA gene-based amplicon sequencing in each group reveled that AB23A not only reduced the abundance of the Firmicutes/Bacteroidaeota ratio and Actinobacteriota/Bacteroidaeota ratio, but regulated the abundance of the top 10 genera, including norank_f__Muribaculaceae, Lactobacillus, Ileibacterium, Turicibacter, Faecalibaculum, the Lachnospiraceae_NK4A136_group, unclassified_f__Lachnospiraceae, and norank_f__Lachnospiraceae. AB23A significantly reduced the serum levels of lipopolysaccharide and branched-chain amino acids, which are positively correlated with the abundances of Ileibacterium and Turicibacter. Moreover, AB23A led to remarkable reductions in the activation of TLR4, NF-κB, and mTOR, and upregulated the expression of tight junction proteins, including ZO-1 and occludin. These results revealed that AB23A displayed a prebiotic capacity in HFD-fed NAFLD mice.

Krill Protein Hydrolysate Provides High Absorption Rate for All Essential Amino Acids-A Randomized Control Cross-Over Trial.

BACKGROUND: adequate protein intake is essential to humans and, since the global demand for protein-containing foods is increasing, identifying new high-quality protein sources is needed. In this study, we investigated the acute postprandial bioavailability of amino acids (AAs) from a krill protein hydrolysate compared to a soy and a whey protein isolate. METHODS: the study was a randomized, placebo-controlled crossover trial including ten healthy young males. On four non-consecutive days, volunteers consumed water or one of three protein-matched supplements: whey protein isolate, soy protein isolate or krill protein hydrolysate. Blood samples were collected prior to and until 180 min after consumption. Serum postprandial AA concentrations were determined using 1H NMR spectroscopy. Hunger and satiety were assessed using visual analogue scales (VAS). RESULTS: whey and krill resulted in significantly higher AA concentrations compared to soy between 20-60 min and 20-40 min after consumption, respectively. Area under the curve (AUC) analyses revealed that whey resulted in the highest postprandial serum concentrations of essential AAs (EAAs) and branched chain AAs (BCAAs), followed by krill and soy, respectively. CONCLUSIONS: krill protein hydrolysate increases postprandial serum EAA and BCAA concentrations in a superior manner to soy protein isolate and thus might represent a promising future protein source in human nutrition.

Determination of Branched-Chain Amino Acids in Food Supplements and Human Plasma by a CE-MS/MS Method with Enhanced Resolution.

In the presented study, a capillary electrophoresis-mass spectrometry method combining high separation efficiency and sensitive detection has been developed and validated, for the first time, to quantify branched chain amino acids (valine, isoleucine, leucine) in commercial food and sport supplement samples and human plasma samples. The separations were performed in a bare fused silica capillary. The background electrolyte was composed of 500 mM formic acid with pH 2.0. The plasma sample pretreatment was realized by simple protein precipitation with acetonitrile. Injection of a short zone of highly basic electrolyte before the sample injection and application of the negative pressure on the separation were accompanied by enhanced resolution of the isobaric amino acids-isoleucine and leucine. The developed method was characterized by favorable validation parameters, such as linearity (r2 > 0.99), accuracy and precision, the limit of detection, lower limit of quantification, or robustness. These parameters were more than sufficient for the quantification of branched chain amino acids in various samples. The determined concentrations of branched chain amino acids in food and sports supplements were in very good agreement with the content declared by the manufacturer. The investigated concentrations of branched chain amino acids were in the range 294.68-359.24 µM for valine, 91.76-95.67 µM for isoleucine, and 196.78-251.24 µM for leucine. These concentrations fall within the physiological limits. The developed CE-MS/MS method represents a suitable alternative to traditional approaches used in branched chain amino acid quality control and bioanalysis.

Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals.

We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. L-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.

Easy clinical predictor for low BCAA to tyrosine ratio in chronic liver disease patients with hepatocellular carcinoma: Usefulness of ALBI score as nutritional prognostic marker.

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis.

Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and branched-chain α-keto acid levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from mice fed an HFHS diet or HFD, but did not worsen insulin resistance. A set of short- and long-chain acyl CoAs were elevated by diet alone in muscle, liver, and white adipose tissue (WAT), but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice, while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on 2 different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.

Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.

Maple syrup urine disease (MSUD) is a genetic disorder that leads the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine, valine and metabolites. The symptomatology includes psychomotor delay and mental retardation. MSUD therapy comprises a lifelong protein strict diet with low BCAA levels and is well established that high concentrations of Leu and/or its ketoacid are associated with neurological symptoms. Recently, it was demonstrated that the phenylbutyrate (PBA) have the ability to decrease BCAA concentrations. This work aimed the development of lipid-based nanoparticles loaded with PBA, capable of targeting to the central nervous system in order to verify its action mechanisms on oxidative stress and cell death in brain of rats subjected to a MSUD chronic model. PBA-loaded nanoparticles treatment was effective in significantly decreasing BCAA concentration in plasma and Leu in the cerebral cortex of MSUD animals. Furthermore, PBA modulate the activity of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes, as well as preventing the oxidative damage to lipid membranes and proteins. PBA was also able to decrease the glial fibrillary acidic protein concentrations and partially decreased the reactive species production and caspase-3 activity in MSUD rats. Taken together, the data indicate that the PBA-loaded nanoparticles could be an efficient adjuvant in the MSUD therapy, protecting against oxidative brain damage and neuroinflammation.

Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet.

BACKGROUND: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. RESULTS: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.

Central Regulation of Branched-Chain Amino Acids Is Mediated by AgRP Neurons.

Circulating branched-chain amino acids (BCAAs) are elevated in obesity and diabetes, and recent studies support a causal role for BCAAs in insulin resistance and defective glycemic control. The physiological mechanisms underlying BCAA regulation are poorly understood. Here we show that insulin signaling in the mediobasal hypothalamus (MBH) of rats is mandatory for lowering plasma BCAAs, most probably by inducing hepatic BCAA catabolism. Insulin receptor deletion only in agouti-related protein (AgRP)-expressing neurons (AgRP neurons) in the MBH impaired hepatic BCAA breakdown and suppression of plasma BCAAs during hyperinsulinemic clamps in mice. In support of this, chemogenetic stimulation of AgRP neurons in the absence of food significantly raised plasma BCAAs and impaired hepatic BCAA degradation. A prolonged fasting or ghrelin treatment recapitulated designer receptors exclusively activated by designer drugs-induced activation of AgRP neurons and increased plasma BCAAs. Acute stimulation of vagal motor neurons in the dorsal motor nucleus was sufficient to decrease plasma BCAAs. Notably, elevated plasma BCAAs were associated with impaired glucose homeostasis. These findings suggest a critical role of insulin signaling in AgRP neurons for BCAA regulation and raise the possibility that this control may be mediated primarily via vagal outflow. Furthermore, our results provide an opportunity to closely examine the potential mechanistic link between central nervous system-driven BCAA control and glucose homeostasis.

The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation.

Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. Clinical studies have reported that bariatric surgery decreases the circulating levels of BCAAs. The objective of this study was to test the hypothesis that reduced BCAA levels contribute to the metabolic improvements of sustained weight loss and improved glucose tolerance after vertical sleeve gastrectomy (VSG). We find that, as in humans, circulating BCAAs are significantly lower in VSG rats and mice. To increase circulating BCAAs, we tested mice with either increased dietary intake of BCAAs or impaired BCAA catabolism by total body deletion of mitochondrial phosphatase 2C (Pp2cm). Our results show that a decrease in circulating BCAAs is not necessary for sustained body weight loss and improved glucose tolerance after VSG.

Safety, Tolerability, and Physiological Effects of AXA1665, a Novel Composition of Amino Acids, in Subjects With Child-Pugh A and B Cirrhosis.

INTRODUCTION: AXA1665 is a novel investigational amino acid (AA) composition specifically designed to impact AA imbalance, ammoniagenesis, and dysregulated anabolic activity associated with cirrhosis. METHODS: This 2-part study examined AXA1665 effects on safety, tolerability, and hepatic/muscle physiology in subjects with Child-Pugh A and B cirrhosis. Part 1 established plasma ammonia and AA concentration baselines with a standardized protein supplement. Part 2 included two 15-day domiciled periods separated by a 14-day washout. In period 1, subjects were randomly distributed to 2 groups: AXA1665 14.7 g t.i.d. (group 1) or control t.i.d. (group 2). In period 2, subjects from group 1 crossed over to control and those in group 2 crossed over to AXA1665 4.9 g t.i.d. All subjects were maintained on standard of care (standardized meals; 30-minute daily, supervised, mandatory physical activity; and daily late-evening snack). RESULTS: In parts 1 and 2, 23 and 17 participants were enrolled, respectively. Dose-dependent increases were observed in plasma concentrations of AXA1665-constituent AAs. Fasted branched-chain AA-to-aromatic AA and valine-to-phenylalanine ratios were both increased (AXA1665 14.7 g t.i.d. control-adjusted change: 44.3% ± 2.7% and 47.2% ± 3.9%, respectively; P < 0.0001). Despite provision of additional nitrogen, mean fasted plasma ammonia concentration at day 15 numerically decreased (-21.1% in AXA1665 14.7 g t.i.d. vs -3.8% in control; P > 0.05). AXA1665 14.7 g t.i.d. produced a leaner body composition and significantly decreased Liver Frailty Index at day 15 vs control (-0.70 ± 0.15 vs -0.14 ± 0.17; P < 0.05). AXA1665 was safe and well tolerated. DISCUSSION: AXA1665 has potential to mitigate core metabolic derangements associated with cirrhosis.

Plasma branched chain amino acids are lower in short-term profound hypothyroidism and increase in response to thyroid hormone supplementation.

Branched chain amino acids (BCAA) are implicated in the pathogenesis of cardiometabolic diseases conceivably by affecting insulin resistance and mitochondrial dysfunction. Circulating BCAA levels may predict (subclinical) atherosclerosis, diabetes and hypertension development but the factors involved in BCAA regulation are incompletely understood. Given the key role of thyroid hormones on many metabolic processes including protein metabolism, we aimed to determine effects of thyroid dysfunction on circulating BCAA. Effects of short-term profound hypothyroidism on plasma BCAA were determined in 17 patients who had undergone total thyroidectomy for differentiated thyroid carcinoma. Patients were studied during hypothyroidism, i.e. after thyroidectomy, and after thyroid hormone supplementation. Plasma BCAA (sum of valine, leucine and isoleucine) and alanine were measured by nuclear magnetic resonance spectroscopy. During hypothyroidism (median thyroid-stimulating hormone 81 (IQR 67-120.5) mU/L), plasma BCAA were lower (255 (IQR 222-289) µmol/L) compared to a euthyroid reference population (n = 5579; 377 µmol/L (2.5th to 97.5th percentile 258-548), p < 0.001). After 20 weeks of thyroid hormone supplementation (thyroid-stimulating hormone 0.03 (IQR 0.01-0.14 mU/L) plasma BCAA had increased (328 (IQR 272-392) µmol/L, p = .001), but plasma alanine concentrations were unaltered (p = .50). Changes in body weight in response to thyroid hormone supplementation were correlated with changes in plasma BCAA (r = 0.721 p = .001, but not with changes in cholesterol or glucose (p > .80). In conclusion, plasma BCAA concentrations are lower during short-term profound hypothyroidism in humans, and increase in response to thyroid hormone supplementation. Changes in BCAA and in body weight after reversal of the hypothyroid state appear to be interrelated.

Net Absorption and Metabolism of ß-Hydroxy- ß-Methyl Butyrate during Late Gestation in a Pig Model.

The leucine metabolite, ß-hydroxy-ß-methyl butyrate (HMB), is widely used in human nutrition and animal production as a nutritional supplement. Although the HMB usage during late gestation has been demonstrated to have a positive effect on fetal development, knowledge on net absorption and metabolism of HMB and impact of HMB on branched chain amino acids (BCAAs) metabolism is lacking. To address this, we conducted a study using pigs during the perinatal period as a model organism. Eight-second parity sows were fitted with indwelling catheters in the femoral artery and in the portal, hepatic, femoral, and mesenteric veins. Eight hourly sets of blood samples were taken starting 30 min before the morning meal on day -10 and day -3 relative to parturition. Four control (CON) sows were fed a standard lactation diet from day -15 and throughout the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)2/kg body weight mixed in one third of the morning meal from day -10 until parturition. Blood gases, plasma metabolites, milk compositions, and apparent total tract digestibility of nutrients were measured. Arterial plasma concentrations of HMB (p < 0.001), Cys (p < 0.001), and Lys (p < 0.10) were increased in HMB supplemented sows, while arterial plasma triglycerides concentration was decreased (p < 0.05). The net portal recovery of Ala and Asp were increased in HMB sows (p < 0.05). Sows fed HMB had increased hepatic vein flow and net hepatic fluxes of Met, Asn, and Gln (p < 0.05). In contrast, the femoral extraction rates of Ala and Ser were decreased by dietary HMB supplementation (p < 0.05). Dietary HMB treatment and sampling time relative to feeding had an interaction on arterial concentrations, net portal fluxes, and femoral extraction rates of BCAAs. The net portal recovery of HMB was 88%, while 14% of supplemented HMB was excreted through urine and 4% through feces. Moreover, the gastrointestinal tract metabolized 8% while the liver metabolized 12%. Finally, 26% of the daily intake of HMB was secreted via colostrum at the day of farrowing. This study demonstrated that dietary HMB supplementation increased net uptake of amino acids and increased fatty acid oxidation through improving blood flow and insulin sensitivity during the late gestation. Most importantly, oral HMB administration could maintain a stable postprandial absorption and altered metabolism in BCAAs. Net portal flux of HMB at 5.5 to 6.5 h after feeding approached zero, indicating that HMB ideally should be administrated two or three times, daily.

Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient improves the branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia: a prospective study.

OBJECTIVE: The present study aimed to elucidate the effect of switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient in patients with cirrhosis with hypoalbuminemia. METHODS: Twenty-six patients with cirrhosis with hypoalbuminemia despite treatment with branched-chain amino acid granules containing 12 g of branched-chain amino acid were enrolled in the prospective study. The branched-chain amino acid-enriched nutrient and control groups were composed of 16 and 10 patients, respectively. The patients in branched-chain amino acid-enriched nutrient group switched to branched-chain amino acid-enriched nutrient mixture containing 12.2 g of branched-chain amino acid and 410 kcal with a half of it consumed as a late evening snack, and the patients in the control group continued branched-chain amino acid granules. Laboratory data related to nutrition parameter were assessed at baseline, 3 months after baseline, and at 6 months after baseline. RESULTS: Two patients were withdrawn; hence, nine and 15 patients in the branched-chain amino acid granules and branched-chain amino acid-enriched nutrient groups, respectively, were subjected to full analysis. Serum albumin levels and total lymphocyte counts in both groups did not change in the study period. The branched-chain amino acid-to-tyrosine ratio in the branched-chain amino acid-enriched nutrient group significantly increased from baseline to 6 months after baseline (P = 0.030), whereas that in the control group did not increase. CONCLUSION: Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrients improves branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia.

Effect of branched-chain amino acid supplementation, dietary intake and circulating levels in cardiometabolic diseases: an updated review.

PURPOSE OF REVIEW: Branched-chain amino acids (BCAAs) are essential amino acids derived from diet. BCAA supplementation has been recommended in elderly and athletes, but recent studies suggest an association between high dietary BCAAs and blood levels of BCAAs with greater risk of cardiometabolic diseases (CMD). This review aims to integrate current epidemiological evidence analyzing the association between BCAAs and related-CMD risk factors. RECENT FINDINGS: Most epidemiological studies consistently show that dietary BCAAs are associated with higher risk of type-2 diabetes (T2D) whereas there is limited evidence related with other cardiovascular risk factors. Evidence also exists showing an association between higher circulating BCAA levels and risk of T2D and cardiovascular disease, and also probably with metabolic syndrome and overweight/obesity. Several clinical trials suggest beneficial cardiometabolic effect of BCAAs supplementation, although with a small sample size and short follow-up. Studies show a weak correlation between dietary BCAAs and circulating BCAA levels. Protein quality sources and whole dietary pattern are key aspects to improve our understanding of the effect of BCAAs as well as factors associated with higher protein needs, such as age or frailty. SUMMARY: Dietary and circulating BCAAs exhibit possible detrimental cardiometabolic effects, but BCAA supplementation may have some positive influence on target groups with nutritional deficiencies.

Impact of Branched-Chain Amino Acid Granule Therapy in Patients with Hepatocellular Carcinoma Who Have Normal Albumin Levels and Low Branched-Chain Amino Acid to Tyrosine Ratios.

Serum albumin has been reported to be a useful indicator of liver function and branched-chain amino acid (BCAA) therapy is associated with a lower incidence of hepatocellular carcinoma (HCC). We investigated the impact of BCAA granule therapy on overall survival and disease-specific survival in patients with normal albumin levels and low BCAA to tyrosine ratio (BTR)s who had treatment-naïve HCC. Overall survival and disease-specific survival was analyzed in 78 patients with HCC who were treated (n = 27) or not treated (n = 51) with BCAAs. Twenty-six patients died during the follow-up period. There were 19, 5, and 2 patients who died due to HCC, hepatic failure, and non-liver-related disease, respectively. Multivariate analysis for factors associated with overall survival indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio [HR], 0.317; 95% confidence interval [CI], 0.123-0.813; P = 0.017). In addition, multivariate analysis using competing risks methods indicated that BCAA therapy is independently associated with reduction of disease-specific mortality (HR, 0.216; 95% CI, 0.068-0.689; P = 0.001). In conclusion, BCAA therapy improved both overall survival and disease-specific survival in HCC patients with low BTRs despite having normal albumin levels.

Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.

BACKGROUND AND AIM: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients. METHODS: We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels. CONCLUSION: Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio.