Plasma Branched-chain Amino Acids Research Articles

The profiling of plasma free amino acids and the relationship between serum albumin and plasma-branched chain amino acids in chronic liver disease: a single-center retrospective study.

It is poorly understood how an imbalance of plasma-free amino acids (PFAAs) occurs and how the imbalance shows an association with the serum albumin (sAlb) level during the progression of chronic liver disease (CLDs). The aim of this study is to elucidate the profiles of PFAAs and the relationship between sAlb and PFAAs in recent patients with CLDs during the progression. We retrospectively evaluated the 1569 data of PFAAs data obtained from 908 patients with various CLDs (CHC, CHB. alcoholic, NAFLD/NASH, PBC, AIH, PSC, and cryptogenic). In total, 1140 data of PFAAs could be analyzed in patients with CLDs dependent of their Child-Pugh (CP) score. Various imbalances in PFAAs were observed in each CLDs during the progression. Univariate and multivariate analysis revealed that among 24 PFAAs, the level of plasma-branched chain amino acids (pBCAAs) was significantly associated with the CP score, especially the sAlb score, in patients with chronic hepatitis C virus (CHC), NAFLD/NASH and PBC. The correlation coefficient values between sAlb and pBCAAs-to-Tyrosine ratio (BTR) in these patients were 0.53, 0.53 and 0.79, respectively. Interestingly, although the pBCAAs in NAFLD/NASH patients varied even when the sAlb was within the normal range, the pBCAAs tended to be low when the sAlb was below the normal range. Although a decrease in the level of pBCAAs was observed during the progression regardless of the CLD etiology, the level of total pBCAAs was independently associated with the sAlb level in the PFAAs of CHC, PBC and NAFLD/NASH. The correlation between sAlb and BTR showed the highest value in PBC patients among the patients with CLDs. A decrease in pBCAAs often occurred in NASH even when the sAlb level was kept in the normal range.

Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes

Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91 μg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 μg/mL, in women (P = 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620 pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women (P < 0.0001); no significant association was found with TNF-α. These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance

Background and aimsAn increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). Methods and resultsWe performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. ConclusionThis study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes

Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.

Increase in branched-chain amino acids due to acidemia in neonatal calves with diarrhoea

The aim of this study was to investigate the relationships between acid-base status and plasma branched-chain amino acids (BCAA) concentration in calves with diarrhoea for intravenous nutrition, especially with amino...

Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes.

Relationship between BCAA and blood pH in diarrheic calves

Neonatal diarrhea leads to overall loss of not only electrolytes and water, but also decreases carbohydrates, lipids, and amino acids in calves. The mean fecal fat content was higher in calves with diarrhea than in healthy calves, and the mean caloric intake from milk was decreased by 31% in diarrheic calves compared with that in healthy calves. The negative energy balance continues during the diarrhea period. In addition, diarrheic calves fall into metabolic acidosis. Several studies have demonstrated that metabolic acidosis activates the catabolism of proteins and oxidation of branched-chain amino acids (BCAA) in muscle. If plasma amino acid profiles of diarrheic calves are similar with those in human with acidemia, more energy may be required for diarrheic calves with acidemia. However, intravenous nutrition for diarrheic calves with proteolysis-induced acidemia is poorly understood. The aim of this study was to investigate the relationship between acid-base status and plasma BCAA concentration in calves with diarrhea. This data may be useful for intravenous nutrition, especially with amino acid solutions, in calves with diarrhea.

Plasma amino acids, adiposity, and weight change after gastric bypass surgery: are amino acids associated with weight regain?

Plasma concentrations of several amino acids (AAs) are positively correlated with obesity. The aim of this study was to examine if selected plasma AAs are associated with weight regain from 2 to 4years after Roux-en-Y gastric bypass (RYGB). In a prospective study with 165 patients, we examined the relationship between plasma aromatic AAs (AAAs), branched chain AAs (BCAAs), and total cysteine (tCys) 2years after RYGB, with BMI at 2years and with weight change from 2 to 4years after surgery. Analyses were adjusted for relevant covariates. The investigated AAs at 2years correlated positively with BMI at 2years (P≤0.003 for all). BCAAs and AAAs at 2years correlated inversely with % weight loss from 0 to 2years (P=0.002 and P=0.001, respectively), while the association was not significant for tCys (r=-0.14, P=0.08). Plasma tCys at 2years correlated positively with BMI at 4years (P=0.010) and with weight regain from 2 to 4years (P=0.015). Plasma AAAs, BCAAs, and tCys at 2years were associated with BMI at 2 years. In addition, plasma AAAs and BCAAs at 2years were associated with weight loss from 0 to 2years, while tCys at 2years was associated with weight regain from 2 to 4years after RYGB. These results suggest that high tCys at 2years may be used as a prognostic marker for future weight regain. The study was registered in ClinicalTrials.gov (NCT0 1270451).

Glucose-mediated inactivation of AMP-activated protein kinase reduces the levels of L-type amino acid transporter 1 mRNA in C2C12 cells

Branched chain amino acids (BCAAs) have protective effects against muscle atrophy. Although plasma BCAA concentrations are higher in patients with diabetes than in healthy subjects, diabetes is related to sarcopenia. We hypothesized that high glucose concentration reduces the quantity of BCAA transporters, and consequently, the effects of BCAAs are diminished despite their high levels. We examined whether glucose reduces the expression of L-type amino acid transporter 1 (LAT1), which transports neutral amino acids, including BCAA, in C2C12 myocytes. Glucose reduced LAT1 mRNA level by 80% in the C2C12 cells, compared with that in the glucose-free control cells. Regarding LAT1-related transporters, glucose also reduced the level of sodium-dependent neutral amino acid transporter 2 mRNA, but not that of 4F2 heavy chain. Although fructose reduced LAT1 mRNA levels, 2-deoxyglucose exhibited low effectiveness in reducing LAT1 mRNA level; galactose and mannitol had no effect. These results suggest a relationship between ATP produced during glycolysis and LAT1 mRNA levels. In fact, the AMP-activated protein kinase (AMPK) inhibitor dorsomorphin reduced LAT1 mRNA levels in the absence of glucose, whereas the AMPK activator 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside increased LAT1 mRNA levels even in the presence of glucose. Consistent with these findings, glucose reduced the levels of phospho-AMPKα (Thr172) compared with that in the glucose-free control. These findings indicate that glucose inactivates AMPK, leading to a reduction in LAT1 mRNA levels in the C2C12 cells. This glucose-induced reduction in LAT1 expression may explain the unresponsiveness to BCAA in the patients with diabetes.

Circulating branched-chain amino acids in children with obstructive sleep apnea

The effects of obstructive sleep apnea (OSA) on the metabolic system are not well understood, especially in children. Recent studies have provided evidence of the modulation of insulin action by branched-chain amino acids (BCAAs) and suggested novel mechanistic relationships between glucose and amino acid metabolic pathways. We hypothesized that plasma BCAA levels may serve as biomarkers of insulin resistance and metabolic dysfunction in children with OSA. A polysomnography was conducted for the diagnosis of OSA in 90 snoring children, in a tertiary hospital. Anthropometric and clinical data were measured and venous blood samples were collected for the measurement of plasma glucose, insulin, HbA1c, and amino acids. Children with OSA had significantly higher levels of BCAAs (leucine, isoleucine, and total BCAAs) compared with those without OSA (P = 0.024). A positive significant correlation was observed between insulin levels and both leucine and isoleucine (r = 0.232; P < 0.05). On multivariate regression analyses, the presence of OSA was significantly associated with leucine, isoleucine, and total BCAA concentrations (P = 0.028), whereas the arousal index was associated with leucine, valine, and total BCAA levels (P = 0.037). The presence of OSA and sleep fragmentation may induce changes in branched-chain amino acid metabolism in snoring children, independently of obesity. These data may suggest a new mechanism linking OSA and glucose homeostasis.

Influence of Amino Acids in Dairy Products on Glucose Homeostasis: The Clinical Evidence.

Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods.

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10-7). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10-6, β 0.96 [95% CI 0.45, 1.47] p = 3 × 10-4, and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). Our results suggest that higher BCAA levels do not have a causal effect on insulin resistance while increased insulin resistance drives higher circulating fasting BCAA levels.

Characterization of a rat model of moderate liver dysfunction based on alpha-naphthylisothiocyanate-induced cholestasis.

Plasma amino acid level changes occur in mild, moderate and severe stages of liver injury in human patients. In animal models, however, data are mainly restricted to severe liver injury models in rats. Here we present the characterization of a rat model of moderate liver dysfunction secondary to alpha-napthylisothiocyanate (ANIT)-induced cholestasis. Rats treated with 30 mg/kg/day ANIT for 3 weeks exhibited a time-dependent increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin levels and a decrease in albumin concentration. According to a liver dysfunction evaluation based on the human Child-Pugh-Score, animals developed a moderate liver dysfunction in the first two weeks of ANIT treatment, while only a mild dysfunction was observed at the end of week 3 despite ongoing ANIT administration. Univariate analysis of branched-chain amino acid plasma levels indicated that reduced levels of branched chain amino acids were associated with the ANIT treatment. These data may set the stage for further research of amino acid disturbances and requirements in non-severe cholestasis.

Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis

Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver–skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity.

Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P < 0.01) whole body phenylalanine rate of appearance (μmol·kg-1·min-1), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA.

Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes.

Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D. We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses' Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010). We documented 16097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta-analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95%confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01). Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D.

Amino acid changes during transition to a vegan diet supplemented with fish in healthy humans

Purpose To explore whether changes in dietary protein sources can lower plasma branched-chain amino acids (BCAAs), aromatic amino acids and sulfur amino acids (SAAs) that are often elevated in the obese, insulin-resistant state and in type 2 diabetes.MethodsThirty-six subjects (mean age 31 ± 2 years) underwent a voluntary abstinence from meat, poultry, eggs, and dairy products for 6 weeks, while enriching the diet with fish, in fulfillment of a religious fast. Subjects were assessed 1 week before the fast (V1), 1 week after initiation of the fast (V2) and in the last week of the fast (V3). Thirty-four subjects completed all three visits.ResultsFasting plasma BCAAs decreased at V2 and remained low at V3 (P < 0.001 for all). Valine showed the greatest decline, by 20 and 19 % at V2 and V3, respectively. Phenylalanine and tryptophan, but not tyrosine, also decreased at V2 and V3. The two proteinogenic SAAs, methionine and cysteine, remained stable, but the cysteine product, taurine, decreased from 92 ± 7 μmol/L to 66 ± 6 (V2; P = 0.003) and 65 ± 6 μmol/L (V3; P = 0.003). A progressive decline in plasma glutamic acid, coupled with an increase in glutamine, was observed. Plasma total and LDL cholesterol decreased at V2 and V3 (P < 0.001 for all).ConclusionChanging dietary protein sources to plant- and fish-based sources in an ad libitum setting lowers the plasma BCAAs that have been linked to diabetes risk. These findings point to habitual diet as a potentially modifiable determinant of fasting plasma BCAA concentrations.

Biochemical and clinical effects of Whey protein supplementation in Parkinson's disease: A pilot study

BackgroundParkinson's disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients, is associated with disease progression and is a marker of oxidative stress. Whey protein is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown that supplementation with Whey protein increases glutathione synthesis and muscle strength. Objectives and methodsIn this study, we conducted a placebo-controlled, double-blind study (NCT01662414) to investigate the effects of undenatured Whey protein isolate supplementation for 6months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical outcome assessments included the unified Parkinson's disease rating scale (UPDRS) and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined before and after supplementation. 15 patients received Whey protein, and 17 received Soy protein, served as a control group. ResultsSignificant increases in plasma concentration of reduced glutathione and the ratio of reduced to oxidized glutathione were found in the Whey-supplemented patients but not in a control group. This was associated with a significant decrease of plasma levels of Hcy. The plasma levels of total glutathione were not significantly changed in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients were not significantly ameliorated in either group. However, significant negative correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented PD patients. ConclusionThis study is the first to report that Whey protein supplementation significantly increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs and EAAs in patients with PD, together with a concomitant significant reduction of plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term, large randomized clinical studies are needed to explore the benefits of Whey protein supplementation in the management of PD patients.

Effects of Increased Plasma Branched-chain Amino Acids and Insulin on Muscle Protein Metabolism

Effects of Increased Plasma Branched-chain Amino Acids and Insulin on Muscle Protein Metabolism

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model.

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset.