Effects Of Branched-chain Amino Acids Research Articles

Effects of branched-chain amino acid supplement on knee peak torque and indicators of muscle damage following isokinetic exercise-induced delayed onset muscle soreness

[Purpose] This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplement on delayed onset muscle soreness (DOMS) by analyzing the maximum muscle strength and indicators of muscle damage.[Methods] Twelve men with majors in physical education were assigned to the BCAA group and placebo group in a double-blinded design, and repeated measurements were conducted. DOMS was induced with an isokinetic exercise. Following BCAA administration, the changes in the knee extension peak torque, flexion peak torque, aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) concentrations were analyzed. The maximum knee muscle strength was measured at the baseline (pre-D0) following BCAA administration for 5 days before exercise (-D5, -4D, -3D, -2D, -1D). In contrast, the post-treatment measurements (D3) were recorded after BCAA administration for 3 days (post-D0, D1, D2). Blood samples were obtained before (pre-D0), immediately after (post-D0), 24 h (D1), 48 h (D2), and 72 h (D3) after the exercise to analyze the indicators of muscle strength. BCAA was administered twice daily for 8 days (5 days and 3 days before inducing DOMS and during the experimental period, respectively).[Results] There was no difference in the flexion peak torque between the groups. However, the BCAA group showed a significantly higher extension peak torque at D3 (second isokinetic exercise), compared to the placebo group (p<.05). There was no difference in AST changes between the groups. Nonetheless, the CK and LDH were significantly reduced in the BCAA group, compared to the placebo group. There was no correlation between the extension peak torque and flexion peak torque. However, the CK and LDH increased proportionately in DOMS. Moreover, their concentrations significantly increased with a decreasing peak torque (p<.01).[Conclusion] An exercise-induced DOMS results in a decrease in the peak torque and a proportional increase in the CK and LDH concentrations. Moreover, the administration of BCAA inhibits the reduction of the extension peak torque and elevation of CK and LDH concentrations. Therefore, BCAA might be administered as a supplement to maintain the muscle strength and prevent muscle damage during vigorous exercises that may induce DOMS in sports settings.

Excessive ROS production and enhanced autophagy contribute to myocardial injury induced by branched-chain amino acids: Roles for the AMPK-ULK1 signaling pathway and α7nAChR

Backgrounds and aimsLeucine, isoleucine, and valine are diet derived and essential amino acids that are termed branched-chain amino acids (BCAA). BCAA are widely used as dietary supplements to boost muscle growth and enhance exercise performance. However, the effects of BCAA on myocardial function are largely unknown. This study was designed to investigate whether BCAA affect heart function and, if so, to further explore the underlying molecular basis for the observed effects. Methods and resultsC57BL/6J mice were randomly divided into two groups, the control group received solvent (water) and the BCAA group received 2% BCAA dissolved in water, for a successive period of 12 weeks. Compared with control, BCAA treatment significantly increased water consumption without changing body weight or diet consumption; heart tissue BCAA levels were increased, markers representative of myocardial injury in heart tissue including c-reactive protein and cardiac muscle troponin were increased ; and creatine kinase, creatine kinase-MB, and lactate dehydrogenase were increased in serum; severe myocardial fibrosis was observed by Masson staining, which was accompanied by increased reactive oxygen species (ROS) production and decreased superoxide dismutase activity in heart tissue; both p-AMPK and p-ULK1 were significantly increased as was autophagy, judged by the presence of LC3 by western blotting and immunofluorescence, increased numbers of autophagosomes were found by transmission electron microscopy in the BCAA group. In vitro, 20 mmol/L BCAA significantly decreased cell viability and increased the production of ROS, as well as the expression of p-AMPK/AMPK and p-ULK1/ULK1 in cultured H9C2 cells. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) improved cell viability and reversed ROS changes. Decreased H9C2 cell viability induced with 20 mmol/L BCAA was reversed by either blocking AMPK or inhibition of ULK1. Furthermore, blocking AMPK significantly decreased p-ULK1/ULK1, while inhibition of ULK1 reversed the enhanced expression of LC3-II/LC3-I induced by BCAA. Excessive ROS production and decreased cell viability induced by BCAA were further confirmed in primary cultured murine cardiomyocytes. Pharmacological activation of α7nAChR with PNU-282987 attenuated BCAA-induced injury in primary murine cardiomyocytes. However, this compound failed to suppress BCAA activation of AMPK and autophagy (LC3-II/I ratio). ConclusionThese results provide the first evidence that treatment of mice with BCAA induced myocardial injury by triggering excessive ROS production and by enhancing AMPK-ULK1 pathway-dependent autophagy. These findings suggested that inhibition of either ROS production or autophagy may alleviate myocardial injury induced by BCAA.

Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells.

Background/AimsPatients with liver cirrhosis (LC) have low levels of branched-chain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti-fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs).MethodsLX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real-time quantitative polymerase chain reaction and Western blotting.ResultsThe increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively.ConclusionsBCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Usefulness of Plasma Branched-Chain Amino Acid Analysis in Predicting Outcomes of Patients with Nonischemic Dilated Cardiomyopathy.

The metabolism of branched-chain amino acids (BCAAs) is reported to change in heart failure (HF) and correlate with cardiac function. However, the effect of BCAAs on HF remains controversial. We investigate the prognostic value of the plasma BCAA level in nonischemic dilated cardiomyopathy (NIDCM).This study enrolled 39 NIDCM patients, who underwent plasma amino acid (AA) analysis. The ratio of BCAAs to total AAs was calculated. All patients were divided into two groups at the median of BCAA/total AA ratio; high BCAA/total AA group (≥ 0.15, n = 20) and low BCAA/total AA group (< 0.15, n = 19). A cardiac event was defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia.The mean age was 51.1 ± 12.3 years and left ventricular ejection fraction (LVEF) was 32.7 ± 10.1%. In the low BCAA/total AA group, the body mass index and the total cholesterol level were lower than in the high BCAA/total AA group. The BCAA/total AA ratio was positively correlated with LVEF (r = 0.35, P = 0.031) and negatively correlated with brain natriuretic peptide (r = -0.37, P = 0.020). The low BCAA/total AA group had a lower cardiac event-free rate (5-year: 100% versus 73%; P = 0.019). In univariate analysis, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (hazard ratio: 0.045, P = 0.0014), hemoglobin (hazard ratio: 0.49 per 1 g/dL, P = 0.0022), and BCAA/total AA ratio < 0.15 (hazard ratio: not available, P = 0.0066) were major predictors for cardiac events.The BCAA/total AA ratio might be a useful predictor for future cardiac events in patients with NIDCM.

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

Background and Aims: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. Methods: Liver cirrhosis patients with Child–Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. Results: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221–0.684, p < 0.001). Conclusion: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

Short-term branched-chain amino acid supplementation does not enhance vertical jump in professional volleyball players. A double-blind, controlled, randomized study.

To the best of the authors' knowledge, no previous studies have described the effect of branched-chain amino acids (BCAA) on vertical performance during a week in professional volleyball players. This study assessed BCAA supplementation for a week, aiming to improve vertical jump performance in male professional volleyball players. Twelve male volleyballers were randomly assigned to a BCAA group (n = 6) or a control group (n = 6). The BCAA group ingested 21 g over a week, 7 g per day on Monday, Wednesday, and Friday, before a volleyball training session, while the control group drank a placebo drink. Participants performed 8 maximal countermovement jumps (CMJ); the 3 CMJs on Monday and Wednesday were evaluated after warm-up, after plyometric training, and at the end of the training session; and the 2 CMJs on Friday were evaluated after warm-up, and at the end of the training session. Compared with baseline, no significant differences in CMJ over the week were observed in BCAA or control group, neither between groups. The results indicated that 21 g of BCAA supplementation over a week did not improve vertical jump performance in professional volleyball players.

Effect of branched chain amino acid supplementation on dialysis adequacy and nutritional parameters in hemodialysis patients.

Malnutrition in hemodialysis (HD) patients is caused by deficient nutrient and protein intake and has a negative impact on patient outcomes. The assessment of dialysis adequacy in these patients depends to a large extent on the calculation of urea clearance using dialyzer clearance of urea (K) multiplied by the duration of the dialysis treatment (t, in minutes) divided by the volume of distribution of urea in the body (V, in mL); Kt/V. This study aims to detect the effect of branched-chain amino acid (BCAA) supplementation on Kt/V and other nutritional parameters such as serum albumin as well as body mass index. Forty-six patients from the HD Unit of Mostafa Mahmoud Hospital were included in this study. Daily intake of BCAA was continued for three months. At the start of the study, before the intervention, and at the end of the 3rd month, we measured serum albumin, valine, leucine, iso-leucine, and Kt/V. Analysis of data was performed using paired and independent t-test. We found that BCAA has a highly significant effect on increasing the level of albumin, leucine, isoleucine, valine, and Kt/V in HD patients (P <0.001) (Paired t-test). BCAA supplements could be used in this patient population to improve dialysis adequacy and outcome.

EXPERIMENTAL SUBSTANTIATION OF THE IMMUNOSTIMULATING EFFECT OF BRANCHED-CHAIN AMINO ACIDS UNDER STRESS

The aim is to study the effect of branched-chain amino acid (BCAA) on cytokine synthesis in male Wistar rats on the background of cyclic starvation. A study of 2 months duration was performed on 60 rats, which were divided into 3 groups (20 rats in each group): rats of the control group (K-group) received standardized balanced laboratory feed for rodents ad libitum. The animals of the 1st experimental group (O-1 group) were fed according to the following scheme: the first day - feed ad libitum, the second and the third day - fasting, the rats of the 2nd experimental group (O-2 group) were given feed according to the same scheme, but with the addition of BCAA at a dosage of 70 mg/kg body weight per day. In the serum of rats, cytokine levels were determined: GM-CSF, INF-γ, IL-10, IL-12p70, IL-13, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL- 6, TNF-α on the Luminex 200 multiplex analyzer (Luminex Corporation, USA). Statistical processing of the results was performed using the IBM SPSS Statistics Version 20.0 application package (“IBM”, USA). As a result of the study, it was established that the consumption of BCAA by rats for 2 months on the background of cyclic starvation causes a decrease in the level of IL-10 and an increase in serum levels of IL-1a and IL-2 due to the activation of signaling pathways that regulate switching of the Th2 immune response to the predominant production of Th1 cytokines.

Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial

ABSTRACTBackgroundProtein ingestion increases muscle protein synthesis rates. However, limited data are currently available on the effects of branched-chain amino acid (BCAA) and branched-chain ketoacid (BCKA) ingestion on postprandial muscle protein synthesis rates.ObjectiveThe aim of this study was to compare the impact of ingesting 6 g BCAA, 6 g BCKA, and 30 g milk protein (MILK) on the postprandial rise in circulating amino acid concentrations and subsequent myofibrillar protein synthesis rates in older males.MethodsIn a parallel design, 45 older males (age: 71 ± 1 y; BMI: 25.4 ± 0.8 kg/m2) were randomly assigned to ingest a drink containing 6 g BCAA, 6 g BCKA, or 30 g MILK. Basal and postprandial myofibrillar protein synthesis rates were assessed by primed continuous l-[ring-13C6]phenylalanine infusions with the collection of blood samples and muscle biopsies.ResultsPlasma BCAA concentrations increased following test drink ingestion in all groups, with greater increases in the BCAA and MILK groups compared with the BCKA group (P < 0.05). Plasma BCKA concentrations increased following test drink ingestion in all groups, with greater increases in the BCKA group compared with the BCAA and MILK groups (P < 0.05). Ingestion of MILK, BCAA, and BCKA significantly increased early myofibrillar protein synthesis rates (0–2 h) above basal rates (from 0.020 ± 0.002%/h to 0.042 ± 0.004%/h, 0.022 ± 0.002%/h to 0.044 ± 0.004%/h, and 0.023 ± 0.003%/h to 0.044 ± 0.004%/h, respectively; P < 0.001), with no differences between groups (P > 0.05). Myofibrillar protein synthesis rates during the late postprandial phase (2–5 h) remained elevated in the MILK group (0.039 ± 0.004%/h; P < 0.001), but returned to baseline values following BCAA and BCKA ingestion (0.024 ± 0.005%/h and 0.024 ± 0.005%/h, respectively; P > 0.05).ConclusionsIngestion of 6 g BCAA, 6 g BCKA, and 30 g MILK increases myofibrillar protein synthesis rates during the early postprandial phase (0–2 h) in vivo in healthy older males. The postprandial increase following the ingestion of 6 g BCAA and BCKA is short-lived, with higher myofibrillar protein synthesis rates only being maintained following the ingestion of an equivalent amount of intact milk protein. This trial was registered at Nederlands Trial Register (www.trialregister.nl) as NTR6047.

Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study

Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism. The aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals. This is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers. BCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA: -3.3%±3%; low-BCAA: 10.0%±6%; P=0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9%±8%; low-BCAA: 14.8%±10%; P=0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0±1 pg/mL; low-BCAA: 5.7±1 pg/mL; P=0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4%±9%; low-BCAA: 29.0%±18%; P=0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4%±187%; low-BCAA: 20.6%±33%; P=0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0%±12%; low-BCAA: 9.2%±11%), valine (BCAA: 9.1%±11%; low-BCAA: 12.0%±13%), or isoleucine (BCAA: 2.5%±11%; low-BCAA: 7.3%±11%). Our data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.

Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling

How individuals respond to chronic stress varies. Susceptible individuals ultimately develop depression; whereas resilient individuals live normally. In this study, our objective was to examine the effect of branched-chain amino acids (BCAA), commonly used by athletes, on susceptibility to stress. Male C57BL/6 mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day11, the behavior of mice was assessed using the social interaction test, elevated plus maze and open field. Mice received the BCAA leucine, isoleucine or valine before each defeat session. Furthermore, we examined whether BCAA regulate brain derived neurotrophic factor (BDNF) signaling by using a brain-permeable tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We also tested the effect of voluntary exercise and high protein diets on susceptibility to stress. Mice exposed to chronic stress displayed increased susceptibility and social avoidance. BCAA promoted resilience to chronic stress, rescued social avoidance behaviors and increased hippocampal BDNF levels and TRKB activation. Inhibition of TRKB signaling abolished the ability of BCAA to promote resilience to stress and to rescue social avoidance. Interestingly, we found that BCAA activate the exercise-regulated PGC1a/FNDC5 pathway known to induce hippocampal BDNF signaling. Although both voluntary exercise and BCAA promoted resilience to stress, combining them did not yield synergistic effects confirming that they affect similar pathways. We also discovered that high protein diets mimic the effect of BCAA by rescuing social deficits induced by chronic stress and increase Bdnf expression in the hippocampus. Our data indicate that BCAA, exercise and high protein diets rescue susceptibility to stress by activating the hippocampal BDNF/TRKB signaling.

Effects of Branched-Chain Amino Acid and Glutamine Supplementation on Angiogenic Factors and Pro-Inflammatory Cytokines after Acute Exercise in Adolescence Athletes

Effects of Branched-Chain Amino Acid and Glutamine Supplementation on Angiogenic Factors and Pro-Inflammatory Cytokines after Acute Exercise in Adolescence Athletes

Effect of branched chain amino acid on apoptosis of neurons after focal cerebral ischemia in rats

Objective To investigate the regulatory effect of branched chain amino acids(BCAA) on the expression of apoptosis related proteins after cerebral ischemia reperfusion injury and the protective effects of BCAA on ischemic brain injury in rats. Methods 40 male SD rats were randomly divided into normal diet group(n=20)and branched chain amino acid (BCAA) group(n=20)according to the random number table, and each group was randomly divided into control group (n=6), sham operation group (n=6) and model group (n=8) which used suture method to make ischemia reperfusion model. After modeling, modified Neurological Severity Scores (mNSS) was used to access the neurological impairment degree of 2, 6, 24, 48 and 72 h in each group. The expression of apoptosis related proteins (Cleaved, Bax/Bcl-2) after 72 h was detected by the method of immune protein imprinting (Caspase3) and compared between normal diet group and BCAA group. Results Compared with the normal diet rats, the mNSS of BCAA diet rats after modeling at 2, 6, 24, 48, 72 h decreased(11.35±2.78 vs. 7.15±2.41, P=0.019; 9.35±1.75 vs. 5.82±1.17, P=0.002; 6.11±1.16 vs. 4.39±1.46, P=0.048; 5.87±1.32 vs. 3.55±1.94, P=0.036; 4.98±2.24 vs. 2.09±1.33, P=0.022). The expression of cleaved caspase3 protein and the ratio of Bax/Bcl-2 decreased in BCAA group. Conclusion BCAA can alleviate the apoptosis of rats after ischemia and reperfusion, reduce the damage of nerve function, and has a positive protective effect on ischemic brain injury. Key words: Branched chain amino acid; Cerebral ischemia reperfusion; Apoptosis

Meta-regression analysis to predict the influence of branched-chain and large neutral amino acids on growth performance of pigs1.

A meta-analysis was conducted to evaluate the effects of branched-chain amino acids (BCAA), their interactions, and interactions with large neutral amino acids (LNAA) to develop prediction equations for growth performance of pigs. Data from 25 papers, published from 1995 to 2018, for a total of 44 trials and 210 observations were recorded in a database. Diets were reformulated using the NRC (2012) loading values to estimate nutrient concentrations. The response variables were average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F). The predictor variables tested included average body weight (BW), crude protein, neutral detergent fiber, Ile:Lys, Leu:Lys, Val:Lys, BCAA:Lys, Ile:Leu, Val:Leu, Ile:Val, (Ile+Val):Leu, Trp:Lys, Leu:Trp, Ile:Trp, Val:Trp, BCAA:Trp, Met:Lys, Leu:Met, Ile:Met, Val:Met, BCAA:Met, His:Lys, Leu:His, Ile:His, Val:His, BCAA:His, Thr:Lys, Leu:Thr, Ile:Thr, Val:Thr, BCAA:Thr, (Phe+Tyr):Lys, Leu:(Phe+Tyr), Ile:(Phe+Tyr), Val:(Phe+Tyr), BCAA:(Phe+Tyr), LNAA:Lys, Leu:LNAA, Ile:LNAA, Val:LNAA, and BCAA:LNAA. Amino acids were expressed on standardized ileal digestible basis. The MIXED procedure of SAS (SAS Institute Inc., Cary, NC) was used to develop the equations. The inverse of squared SEM was used to account for heterogeneous errors using the WEIGHT statement. Models were selected with a step-wise manual forward selection. In order to be included in the final model, predictor variables had to be statistically significant (P < 0.05) and provide an improvement of at least 2 points in Bayesian information criterion. The optimum equations were: ADG, g = - 985.94 + (15.2499 × average BW (kg)) - (0.08885 × average BW × average BW) + (1.063 × Leu:Lys) + (20.2659 × Ile:Lys) - (0.1479 × Ile:Lys × Ile:Lys) + (9.2243 × (Ile+Val):Leu) - (0.03321 × (Ile+Val):Leu × (Ile+Val):Leu) - (0.4413 × Ile:Trp); G:F, g/kg = 648.3 - (6.2974 × average BW (kg)) + (0.02051 × average BW × average BW) + (0.5396 × Ile:Lys) + (1.7284 × Val:Lys) - (0.00795 × Val:Lys × Val:Lys) - (1.7594 × Met:Lys); and ADFI, kg = predicted ADG/predicted G:F. Overall, the prediction equations suggest that increasing Leu:Lys negatively impacts ADG due to a reduction in G:F and ADFI caused by insufficient levels of other BCAA and LNAA relative to Leu. According to the model, the addition of Val, Ile, and Trp, alone or in combination, has the potential to counteract the negative effects of high dietary Leu concentrations on growth performance.

Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy.

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis. Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls. Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans.

The Effect of Branched-Chain Amino Acids, Citrulline, and Arginine on High-Intensity Interval Performance in Young Swimmers.

High-intensity interval training has drawn significant interest for its ability to elicit similar training responses with less training volume compared to traditional moderate-intensity protocols. The purpose of this study was to examine the effect of co-ingestion of branched-chain amino acids (BCAA), arginine, and citrulline on 8 × 50 m high-intensity interval swim performance in trained young swimmers. This study used a randomized cross-over design. Eight male (age 15.6 ± 1.3 years) and eight female (age 15.6 ± 0.9 years) swimmers completed both amino acids (AA) and placebo (PL) trials. The participants ingested 0.085 g/kg body weight BCAA, 0.05 g/kg body weight arginine and 0.05 g/kg body weight citrulline before the swim test in the AA trial. The average 50 m time was significantly shorter in the AA trial than that in the PL trial. The AA trial was faster than the PL trial in the first, second, and the seventh laps. The AA trial showed significantly higher plasma BCAA concentrations and lower tryptophan/BCAA ratio. The other biochemical parameters and ratings of perceived exertion were similar between the two trials. The results showed that BCAA, arginine, and citrulline, allowed the participants to swim faster in a high-intensity interval protocol in young swimmers.

Effects of branched-chain amino acids and vitamin D supplementation on physical function, muscle mass and strength, and nutritional status in sarcopenic older adults undergoing hospital-based rehabilitation: A multicenter randomized controlled trial.

To investigate the effects of branched-chain amino acids and vitamin D supplementation on physical function, muscle strength, muscle mass, and nutritional status in sarcopenic older adults undergoing hospital-based rehabilitation. We carried out an 8-week, multicenter, randomized, controlled, blinded outcome, two-cohort parallel group intervention trial of sarcopenic older adults undergoing in-hospital rehabilitation. The eligibility criteria included older adults (aged ≥65 years) with low muscle strength (handgrip strength) and low muscle mass (calf circumference) according to the cut-off values for older Asians. The intervention group received branched-chain amino acids and vitamin D supplementation, whereas the control group did not. Both groups underwent low-intensity resistance training in addition to the post-acute rehabilitation program. The primary outcome of physical function (Functional Independence Measure-motor scores), and the secondary outcomes of muscle strength (handgrip strength), muscle mass (calf circumference) and nutritional status (body mass index) were measured at baseline and at the end of the intervention. Finally, a total of 68 patients were analyzed (intention-to-treat analysis): 35 in the intervention group and 33 in the control group. Functional Independence Measure-motor scores increased significantly in both groups over time (P < 0.05). However, no treatment-by-time effects were observed (median estimated difference 2.4, 95% confidence interval -1.2 to 7.1). Handgrip strength, calf circumference and body mass index increased significantly in both groups over time (P < 0.05), with significantly greater improvements in the intervention group (P = 0.041, 0.033 and 0.035, respectively). We showed that an 8-week intervention of branched-chain amino acids and vitamin D supplementation with low-intensity resistance training improves muscle-related outcomes in sarcopenic older adults undergoing hospital-based rehabilitation (UMIN000006238). Geriatr Gerontol Int 2019; 19: 12-17.

Effect of Branched-Chain Amino Acid Supplementation on Recovery Following Acute Eccentric Exercise.

This study investigated the effect of branched-chain amino acid (BCAA) supplementation on recovery from eccentric exercise. Twenty males ingested either a BCAA supplement or placebo (PLCB) prior to and following eccentric exercise. Creatine kinase (CK), vertical jump (VJ), maximal voluntary isometric contraction (MVIC), jump squat (JS) and perceived soreness were assessed. No significant (p > 0.05) group by time interaction effects were observed for CK, soreness, MVIC, VJ, or JS. CK concentrations were elevated above baseline (p < 0.001) in both groups at 4, 24, 48 and 72 hr, while CK was lower (p = 0.02) in the BCAA group at 48 hr compared to PLCB. Soreness increased significantly from baseline (p < 0.01) in both groups at all time-points; however, BCAA supplemented individuals reported less soreness (p < 0.01) at the 48 and 72 hr time-points. MVIC force output returned to baseline levels (p > 0.05) at 24, 48 and 72 hr for BCAA individuals. No significant difference between groups (p > 0.05) was detected for VJ or JS. BCAA supplementation may mitigate muscle soreness following muscle-damaging exercise. However, when consumed with a diet consisting of ~1.2 g/kg/day protein, the attenuation of muscular performance decrements or corresponding plasma CK levels are likely negligible.

Branched-Chain Amino Acids Enhance Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Transection in Rats

ABSTRACT Purpose This study’s aim was to investigate the beneficial effects of branched-chain amino acids (BCAAs) on the neuronal survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) transection. Method The experimental rats received daily BCAA injections through the caudal vein after left intra-orbital ON transection. Neuroprotection was evaluated by counting Fluorogold-labeled RGCs. The role of mammalian target of rapamycin (mTOR) pathway activation in promoting RGC survival was studied after rapamycin administration. Moreover, a peripheral nerve (PN) graft was transplanted onto the transected ON to study the effects of BCAAs on axon regeneration of injured RGCs. Results Our results showed that BCAAs alleviated the death of RGCs 7 and 14 days after ON transection, accompanied by an activation of mTOR pathway in RGCs. Blocking mTOR pathway with rapamycin eliminated such neuroprotective effects of BCAAs. Moreover, BCAAs also promoted axon regeneration of injured RGCs into a PN graft. Conclusion Our results suggest a neuroprotection of BCAAs through the activation of mTOR pathway. BCAAs also have a beneficial effect on axon regeneration of injured RGCs. Therefore, BCAAs could be considered for the clinical treatment of ON injury.

PPAR\u03b3/Pgc-1\u03b1-Fndc5 pathway up-regulation in gastrocnemius and heart muscle of exercised, branched chain amino acid diet fed mice

BackgroundPrevious studies have revealed the inductive effect of branched-chain amino acids (BCAAs) catabolism on fatty acid oxidation and metabolism, especially in muscle cells. In the present investigation, we have attempted to address whether a combination of BCAAs supplement consumption with aerobic exercise could elaborate the expression of PPARγ, Pgc-1α and Fndc5 genes in gastrocnemius muscle and heart tissue of male C57BL/6 mice.MethodsThirty-six young male mice with an average weight of 18 ± 2 g were selected. Mice were randomly assigned to 6 groups: 20 mg/mL of BCAAs consumption with simultaneous exercise-training, 60 mg/mL of BCAAs consumption with simultaneous exercise-training, exercise-trained with no BCAAs consumption group, 20 mg/mL BCAAs without exercise-training, 60 mg/mL BCAAs without exercise-training, and untrained mice without BCAAs consumption.ResultsThe findings showed a combination of 20 mg/mL BCAAs with aerobic exercise significantly increased Fndc5, PPARγ, Pgc-1α gene expression in skeletal muscles although, circulating Irisin levels remained unchanged (p < 0.05). Interestingly, plasma urea and lactate levels were significantly increased in 60 mg/mL BCAAs administrated mice which performed exercised (p < 0.05). Two-way analysis of variance (ANOVA) was used to examine significant difference between groups and sedentary group.ConclusionsResults showed inductive effect of 20 mg/mL BCAAs on expression levels of Fndc5, PPARγ, Pgc-1α in gastrocnemius muscle similar with counterparts in heart tissue. Of note, higher serum irisin levels were detected after 20 mg/mL BCAAs supplementation coincided with the exercise.Graphical abstractAn Overview on supplemantaion of branched chain amoinoacids on metablism of skeletal muscle and heart