Branched-chain Amino Acids Group Research Articles

Reduced Branched-Chain Amino Acid Intake Improved High-Fat Diet-Induced Nonalcoholic Fatty Pancreas Disease in Mice.

To explore the effects of branched-chain amino acids (BCAAs) on nonalcoholic fatty pancreas disease (NAFPD) and its possible mechanism in high-fat diet (HFD) induced mice. Pancreatic morphology and lipid infiltration was assessed by hematoxylin-eosin staining and immunohistochemistry, and lipid levels in the pancreas were determined using colorimetric enzymatic method. Relevant mechanism was investigated using western blotting and biochemical test. In HFD-fed mice, dietary BCAAs restriction could attenuate body weight increase, improve glucose metabolism, and reduce excessive lipid accumulation in the pancreas. Furthermore, expression of AMPKα and downstream uncoupling protein 1 were upregulated, while genes related to mammalian target of rapamycin complex 1 (mTORC1) signal pathway and lipid de novo synthesis were suppressed in HFD-BCAA restriction group compared with HFD and HFD-high BCAAs fed mice. In addition, BCAA restriction upregulated expression of BCAAs related metabolic enzymes including PPM1K and BCKDHA, and decreased the levels of BCAAs and branched chain keto acid in the pancreas. However, there was no difference in levels of lipid content in the pancreas and gene expression of AMPKα and mTORC1 between HFD and HFD-high BCAAs groups. Branched-chain amino acid restriction ameliorated HFD-induced NAFPD in mice by activation of AMPKα pathway and suppression of mTORC1 pathway.

Effect of a single intravenous injection of branched chain amino acids on body temperature of cats undergoing general anesthesia

ObjectiveTo evaluate the effect of a single intravenous injection of branched chain amino acids (BCAAs) on body temperature in cats undergoing general anesthesia. Study designProspective, blinded, randomized, crossover, experimental study. AnimalsA total of 10 healthy adult cats (five female and five male). MethodsCats were anesthetized three times with three different treatments in a random order: 3 mL kg–1 lactated Ringer’s solution (LRS), 100 mg kg–1 BCAAs (B100) or 200 mg kg–1 BCAAs (B200) solution immediately before induction of anesthesia. After induction, rectal temperature was measured every 5 minutes. Blood samples were collected for the measurement of blood glucose (BG) just before induction, at the end of the 90 minute period of anesthesia, and 24 hours after anesthesia induction. The differences between baseline and each subsequent rectal temperature, and BG measurements were analyzed. Areas under the curve (AUCs) for temperature differences were calculated for each animal for the anesthetic period (AUCT0–90). Parametric or nonparametric data were analyzed by one-way repeated measures anova or Friedman test. A value of p < 0.05 was considered significant. ResultsThere were no significant differences in AUCT0–90 between groups: 41.6 ± 7.7 for LRS, 43.4 ± 6.9 for B100 and 42.9 ± 7.5 for B200 (p = 0.368). No significant differences were observed in BG between groups at 90 minutes and 24 hours after anesthesia induction (p = 0.283 and p = 0.089, respectively). The incidence of hypoglycemia [BG ≤ 3.17 mmol L–1 (57 mg dL–1)] after anesthesia tended to be higher in both B100 (4/10 cats) and B200 groups (3/10 cats) than in LRS group (1/10 cats). Conclusions and clinical relevanceA single, preanesthetic intravenous injection of BCAAs did not attenuate heat loss during anesthesia. More cats were hypoglycemic in the BCAA groups than in the LRS group.

The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Controlled Trial.

Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched-chain amino acids (BCAAs) have been shown to have advantageous effects on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA and exercise may exert synergized effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism toward enhanced synthesis of kynurenic acid, thereby reducing fatigue. This randomized, double-blind, placebo-controlled trial aims to compare the effects of acute (approximately 45 min) and chronic (8 wk) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesized outcomes are modulated by changes in kynurenine metabolism in 30 older adults (n=15, 50% per group). Older adults (aged 60-80 y) who do not exercise >2 days per week and self-report fatigue (≥3 on a scale of 1-10) will be recruited. Participants will be randomized to either the exercise+BCAA group or exercise+placebo group. Participants will engage in high-volume, moderate-intensity, whole-body exercise training (aerobic and resistance exercise; either in-person or web-based sessions) 3 times per week for 8 weeks. In addition, participants will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 mL of water and 2.5 g of a calorie-free water flavor enhancer. Muscle biopsies will be collected before and after the intervention after a 12-hour fast to examine changes in the biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and physical fatigue and metabolism after the 8-week exercise training between the 2 groups. Mental and physical fatigue will be measured before and after the intervention. Mental fatigue will be subjectively assessed through the completion of validated questionnaires. Physical fatigue will be measured by isometric handgrip, 1-repetition maximum, chair rise, 400-meter walk, and cardiopulmonary exercise tests. The study was funded in March 2022, with an anticipated projected data collection period lasting from January 2023 through December 2023. The discovery that kynurenine concentrations are associated with fatigue and are responsive to BCAA supplementation during exercise training could have important implications for the development of future interventions, both lifestyle and pharmacologic, to treat fatigue in older adults. ClinicalTrials.gov NCT05484661; https://www.clinicaltrials.gov/study/NCT05484661. DERR1-10.2196/52199.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83-93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p < 0.03] and Mean Cell haemoglobin Concentration (MCHC) [F = 10, 323; p < 0,0001] showed significant effects of time group. Our findings demonstrate that a long-term intervention with BCAA plus MEP did not lead to significant alterations in the haematological profile. An 8-week withdrawal from interventions did not affect the frailty status in the MEP and MEP + BCAA groups, whereas the control group exhibited an increase in PF status. The findings, demonstrating the potential pro-immune effect and maintenance of MCH and MCHC levels, highlight the relevance of incorporating exercise and nutritional strategies to promote healthy aging. This study contributes to the achievement of the United Nations Sustainable Development Goals 3 (good health and well-being) and 10 (reduced Inequalities) for all.

Effects of branched-chain amino acids supplementation on patients undergoing hepatic intervention: a meta-analysis of randomised controlled trials.

The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.

Early administration of postoperative BCAA-enriched PPN may improve lean body mass loss in gastric cancer patients undergoing gastrectomy

BackgroundIt has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss.MethodsWe conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery.ResultsAt postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (− 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups.ConclusionOur RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.

Effects of branched-chain amino acid supplementation on skeletal muscle proteolytic pathways after exercise-induced muscle injury in rats

To explore the role of branched-chain amino acid(BCAA) supplementation on muscle damage and the regulation of Krüppel-like factor 15(KLF15) and nuclear factor kappa B(NF-κB) mediated proteolytic pathways after an acute eccentric exercise. Male SD rats were divided into placebo group(PLA) and BCAA group(BCAA) randomly, 32 rats per group. Both group were then placed into subgroups: placebo and pre-exercise group(PC), placebo and immediately after exercise group(PE), placebo and 6 h after exercise group(PE6), placebo and 12 h after exercise group(PE12), BCAA and pre-exercise group(BC), BCAA and immediately after exercise group(BE), BCAA and 6 h after exercise group(BE6), BCAA and 12 h after exercise group(BE12), 8 rats per group. Rats in BCAA groups were supplied with BCAA(1 g/(kg·d·BW), 3 days) before the exercise day and placebo groups with equal volume of distilled water. The exercised groups performed a 2 h eccentric exercise on treadmill(16 m/min, -16° slope). Blood and gastrocnemius were collected according to the time points. RT-qPCR was used to measure the mRNA expression of KLF15, NF-κB, FoxO1, Atrogin-1 and MuRF1 in gastrocnemius. (1) No damage was found in myocytes of BC and PC group. The process of morphological damage in BCAA group was relatively faster. (2) The mRNA expression levels of KLF15, FoXO1, Atrogin-1 and MuRF1 in PE were higher than those in PC(P&lt;0.05, P&lt;0.01), NF-κB and Atrogin-1 in PE12 were higher than those in PC(P&lt;0.05). The mRNA expression levels of FoXO1 in BE were higher than those in BC(P&lt;0.05). Compared with PE, the mRNA expression levels of KLF15, Atrogin-1 and MuRF1 in BE were lower(P&lt;0.05, P&lt;0.01), NF-κB and Atrogin-1 in BE12 were lower than those in PE12(P&lt;0.05). The level of serum 3-MH in PE12 group was higher than that in PC group(P&lt;0.05). The proteolysis of skeletal muscle after high-intensity eccentric exercise is mediated by two different pathways: KLF15 and NF-κB, whose activation is time-dependent. BCAA may reduce skeletal muscle proteolysis by lowering the level of gene transcription in the KLF15 and NF-κB related protein degradation pathway, which occurs immediately after exercise.

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study.

Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age < 65 years) with severe obesity (BMI > 35 kg/m2) during weight loss. We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): -2.46 ± 3.04; MM (%): -0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): -2.75 ± 5.98, p = 0.734; MM (%): -0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): -1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary.

Management of minimal and overt hepatic encephalopathy with branched-chain amino acids: a review of the evidence.

Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.

Effect and feasibility of the combination of branched chain amino acid and exercise therapy on muscle mass and echo intensity of muscle in orthopedic patients in a convalescent rehabilitation hospital: A crossover trial.

This study examined the feasibility of nutritional support combined with exercise intervention for restoring muscle and physical functions in convalescent orthopedic patients. We used a crossover design in which nutritional support combined with exercise intervention was administered daily during the early (1 month) and late (1 month) cycles with a 1-week washout period. The exercise intervention was performed twice daily for 2 months in the early and late groups. The exercise intervention consisted of one set of muscle strength, stretching, and physical activity exercises for 20 min each. Nutritional interventions were administered immediately after the exercise. A 3.4 g of branched-chain amino acid supplements (BCAAs) or 1.2 g of starch was ingested. We measured the skeletal muscle mass and isometric muscle strength of the limbs and performed balance tests. After the crossover, the BCAA and Placebo groups were compared. The ratio of improvement in the echo intensity of the rectus femoris (RF) was significantly higher in the BCAA group. A comparison of the order of nutritional intervention showed a significant effect on the RF echo intensity in both groups only when BCAAs were administered. This study's results suggest that the proposed combined intervention improves muscle quality and mass in convalescent orthopedic patients.

Branched-chain amino acids supplementation improves liver frailty index in frail compensated cirrhotic patients: a randomized controlled trial

BackgroundPhysical frailty is related with morbidity and mortality in patients with cirrhosis. Currently, there is no approved treatment of frailty in these patients. Here, we evaluated the efficacy of 16 weeks branched-chain amino acids (BCAA) supplementation on frailty in frail compensated cirrhotic patients.MethodsAfter a 4-week run-in period consisted of dietary and exercise counseling, compensated cirrhotic patients with frailty, defined by liver frailty index (LFI)≥4.5, were randomly assigned (1:1) to BCAA or control group. The BCAA group received twice daily BCAAs supplementation (210 kcal, protein 13.5 g, BCAA 2.03 g) for 16 weeks. The primary outcome was frailty reversion. The secondary outcomes were changes in biochemistries, body composition evaluated by bioelectrical impedance analysis, and quality of life (QoL).Results54 patients were prospectively enrolled (age 65.5 ± 9.9 years, 51.9% female, Child-Pugh A/B 68.5%/31.5%, MELD 10.3 ± 3.1). Baseline characteristics were similar between both groups. At week 16, BCAA group had a significant improvement in LFI (-0.36 ± 0.3 vs. -0.15 ± 0.28, P = 0.01), BMI (+ 0.51 ± 1.19 vs. -0.49 ± 1.89 kg/m2, P = 0.03), and serum albumin (+ 0.26 ± 0.27 vs. +0.06 ± 0.3 g/dl, P = 0.01). The proportion of frailty reversion at week 16 was significantly higher in BCAA group (36% vs. 0%, P < 0.001). Compared with baseline, BCAA group had a significant increase in skeletal muscle index (7.5 ± 1.6 to 7.8 ± 1.5 kg/m2, P = 0.03). Regarding the QoL, only the BCAA group had a significant improvement in all 4 domains of physical component score of the SF-36 questionnaire.ConclusionsA 16-week BCAA supplementation improved frailty in frail compensated cirrhotic patients. In addition, this intervention resulted in an improvement of muscle mass and physical domain of QoL in these patients.Trial registrationThis study was registered with Thai Clinical Trial Registry (TCTR20210928001; https://www.thaiclinicaltrials.org/#).

The effects of arginine and branched-chain amino acid supplementation to reduced-protein diet on intestinal health, cecal short-chain fatty acid profiles, and immune response in broiler chickens challenged with Eimeria spp.

We investigated the effects of supplementing arginine (Arg) and branched-chain amino acids (BCAA) in broilers fed reduced-protein diets and challenged with Eimeria spp. All birds were fed the same starter diet meeting Cobb 500 nutrient specifications from d 1 to 9. Four grower diets: positive control (PC) with 20.0% crude protein (CP); reduced-protein negative control (NC) with 17.5% CP; or NC supplemented with Arg or BCAA at 50% above recommendations (ARG or BCAA) were fed to the birds from d 9 to 28. Birds were allocated in a 2×4 factorial arrangement (4 diets, each with or without challenge), with 8 replicates per treatment. On d 14, the challenge groups were orally gavaged with mixed Eimeria spp. Intestinal permeability was higher (P < 0.05) in NC than PC, whereas the permeability of ARG and BCAA groups did not differ significantly from PC. On d 28, a significant interaction (P < 0.01) was observed in CD8+: CD4+ ratios in cecal tonsils (CT), Eimeria challenge increased the ratios in all groups except for the ARG group. On d 21, a significant interaction was found for CD4+CD25+ percentages in CT (P < 0.01) that Eimeria challenge increased the percentages only in PC and NC groups. On d 21 and 28, significant interactions (P < 0.01) were found for macrophage nitric oxide (NO) production. In nonchallenged birds, NO was higher in the ARG group than other groups, but in challenged birds, NO was higher in both ARG and BCAA groups. On d 21, a significant interaction was found for bile anticoccidial IgA concentrations (P < 0.05) that Eimeria challenge increased IgA only in NC and ARG groups. The results suggest that a reduced-protein diet exacerbates the impact of the Eimeria challenge on intestinal integrity, but this could be mitigated by Arg and BCAA supplementations. Arginine and BCAA supplementations in reduced-protein diets could be beneficial for broilers against Eimeria infection by enhancing the immune responses. The beneficial effects of Arg supplementation tended to be more pronounced compared to BCAA supplementation.

The effects of vitamin B6 on the nutritional support of BCAAs-enriched amino acids formula in rats with partial gastrectomy

Total parenteral nutrition with the formula of amino acids enriched branched-chain amino acids (BCAAs) could promote patients' recovery after gastrointestinal surgery. Previous studies reported that vitamin B6 could promote amino acid metabolism and enhance protein synthesis. The aim of this study was to determine if the addition of vitamin B6 to BCAAs-enriched formula can enhance postoperative nutritional status and intestinal function in rats undergoing partial gastrectomy, and the appropriate compatibility concentration of vitamin B6. Fifty-six male rats were randomly divided into seven groups (n=8 per group): (I) Control, (II) BCAAs-enriched formula group (BCAA), (III) BCAA plus vitamin B6 (50mg/L), (IV) BCAA plus vitamin B6 (100mg/L), (V) BCAA plus vitamin B6 (200mg/L), (VI) BCAA plus vitamin B6 (500mg/L), and (VII) BCAA plus vitamin B6 (1000mg/L). All animals were performed partial gastrectomy and placed a jugular vein catheter. During enteral nutrition, blood and urine samples were repeatedly collected. Gastrocnemius muscle and small intestine were also collected at the end of experiment. The addition of vitamin B6 to BCAAs-enriched formula improved negative nitrogen balance after gastrectomy compared to the BCAAs-enriched formula group at POD1 (first postoperative day) and POD3 (third postoperative day), and 100mg/L was an appropriate concentration of vitamin B6 to enhance the effects of BCAAs-enriched formula. The 3-methylhistidine/creatinine in BCAA plus vitamin B6 groups were significantly lower than that in the BCAA group at POD3. Moreover, BCAA plus vitamin B6 group significantly increased the cross-sectional area of the muscle fibers compared to the BCAA group. Transcriptome sequencing, GO and KEGG enhancement analysis also showed that BCAA plus vitamin B6 group showed muscle organ development and PI3K/AKT pathway enhancement compared to BCAA group. Moreover, AKT/mTOR/4EBP1 pathway was activated in BCAA plus vitamin B6 group. In addition, the results also showed that BCAA plus vitamin B6 decreased D-lactate, and exerted synergistic effects on intestinal morphology. The addition of vitamin B6 to BCAAs-enriched formula could improve nitrogen balance, promote muscle protein synthesis through AKT/mTOR/4EBP1 pathway, and alleviate intestinal mucosa damage after partial gastrectomy in rats. Overall, the results from this pre-clinical study support the use of vitamin B6 as an ingredient to BCAAs-enriched formula, and 100mg/L may be an optimal concentration for rats.

Branched-chain amino acids plus vitamin D supplementation promote increased muscle strength following lumbar surgery for lumbar spinal stenosis: a randomized trial

BACKGROUND CONTEXTAdequate nutrition is essential to address the surgical stress response and mitigate loss of muscle mass, strength, and functionality in older adults with lumbar spinal stenosis (LSS). However, it is unknown whether amino acids and/or vitamin D are beneficial in older adults following lumbar surgery for LSS. PURPOSETo evaluate whether branched-chain amino acids (BCAA) plus vitamin D supplementation could attenuate the loss of muscle mass and strength, accelerate the return of functional mobility, and improve clinical outcomes following lumbar surgery for LSS. STUDY DESIGN/SETTINGA single-center, single-blind randomized controlled trial. PATIENT SAMPLEEighty patients who received lumbar surgery for LSS. OUTCOME MEASURESThe primary outcome was the Zurich claudication questionnaire (ZCQ), and secondary outcomes included knee muscle strength, muscle mass measured by bioelectrical impedance analysis, gait speed and a timed up-and-go test (TUG) at 12 weeks postoperatively. Follow-up assessment was performed for the ZCQ at 52 weeks postoperatively. METHODSPatients ingested the supplementation (BCAA group: BCAA plus vitamin D, Nonamino acid group: nonamino acid) twice daily for 3 weeks from the day after surgery, and received two hours of postoperative inpatient rehabilitation 5 times a week. RESULTSNo significant differences were observed in the mean changes on the ZCQ between the two groups at 12 weeks and 52 weeks. At 2 weeks postoperatively, the nonamino acid group showed significant deterioration compared with the BCAA group for strengths of knee extensor and knee flexor (p < .01). At 12 weeks, the BCAA group showed significant improvements in knee extensor strength and knee flexor strength compared with the nonamino acid group (p <.01). There were no significant differences in mean changes of muscle mass, maximum gait speed, and TUG at 12 weeks between two groups. CONCLUSIONSBCAA plus vitamin D supplementation did not improve LSS-related clinical outcomes after lumbar surgery for LSS, even though muscle strength increased. Future studies should focus on long-term outcomes for muscle mass and physical function, including development of sarcopenia and frailty.

The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

Preoperative administration of branched-chain amino acids reduces postoperative insulin resistance in rats by reducing liver gluconeogenesis

BackgroundPostoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism.Methods and resultsRats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps < 0.05).ConclusionsThis study revealed that BCAA lower blood glucose levels by reducing liver gluconeogenesis without significant elevation of plasma insulin levels. We anticipate that preoperative BCAA supplementation may be a means for preventing postoperative insulin resistance.

Branched-chain amino acid supplementation suppresses the detraining-induced reduction of mitochondrial content in mouse skeletal muscle.

Exercise training enhances oxidative capacity whereas detraining reduces mitochondrial content in skeletal muscle. The strategy to suppress the detraining-induced reduction of mitochondrial content has not been fully elucidated. As previous studies reported that branched-chain amino acid (BCAA) ingestion increased mitochondrial content in skeletal muscle, we evaluated whether BCAA supplementation could suppress the detraining-induced reduction of mitochondrial content. Six-week-old male Institute of Cancer Research (ICR) mice were randomly divided into four groups as follows: control (Con), endurance training (Tr), detraining (DeTr), and detraining with BCAA supplementation (DeTr + BCAA). Mice in Tr, DeTr, and DeTr + BCAA performed treadmill running exercises [20-30 m/min, 60 min, 5 times/week, 4 weeks]. Then, mice in DeTr and DeTr + BCAA were administered with water or BCAA [0.6mg/g of body weight, twice daily] for 2 weeks of detraining. In whole skeletal muscle, mitochondrial enzyme activities and protein content were decreased after 2 weeks of detraining, but the reduction was suppressed by BCAA supplementation. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content, a master regulator of mitochondrial biogenesis, was decreased by detraining irrespective of BCAA ingestion. Regarding mitochondrial degradation, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a mitophagy-related protein, was significantly higher in the Tr group than in the DeTr + BCAA group, but not different from in the DeTr group. With respect to mitochondrial quality, BCAA ingestion did not affect oxygen consumption rate (OCR) and reactive oxygen species (ROS) production in isolated mitochondria. Our findings suggest that BCAA ingestion suppresses the detraining-induced reduction of mitochondrial content partly through inhibiting mitophagy.

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

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

Effects of Branched-Chain Amino Acids on Skeletal Muscle, Glycemic Control, and Neuropsychological Performance in Elderly Persons with Type 2 Diabetes Mellitus: An Exploratory Randomized Controlled Trial.

Although branched-chain amino acids (BCAA) are known to stimulate myofibrillar protein synthesis and affect insulin signaling and kynurenine metabolism (the latter being a metabolite of tryptophan associated with depression and dementia), the effects of BCAA supplementation on type 2 diabetes (T2D) are not clear. Therefore, a 24-week, prospective randomized open blinded-endpoint trial was conducted to evaluate the effects of supplementation of 8 g of BCAA or 7.5 g of soy protein on skeletal muscle and glycemic control as well as adverse events in elderly individuals with T2D. Thirty-six participants were randomly assigned to the BCAA group (n = 21) and the soy protein group (n = 15). Skeletal muscle mass and HbA1c, which were primary endpoints, did not change over time or differ between groups. However, knee extension muscle strength was significantly increased in the soy protein group and showed a tendency to increase in the BCAA group. Homeostasis model assessment for insulin resistance did not significantly change during the trial. Depressive symptoms were significantly improved in the BCAA group but the difference between groups was not significant. Results suggested that BCAA supplementation may not affect skeletal muscle mass and glycemic control and may improve depressive symptoms in elderly individuals with T2D.

Omega-3 fatty acids enhance the beneficial effect of BCAA supplementation on muscle function following eccentric contractions.

ABSTRACTBackgroundThis study investigated the combined effect of branched-chain amino acids (BCAA) and fish oil (FO) on muscle damage caused by eccentric contractions (ECCs) of the elbow flexors, with a special focus on muscular function.MethodsTwenty-nine untrained male participants were enrolled in this double-blind, placebo-controlled, parallel study. The participants were randomly assigned to the placebo (PL) group (n = 9), BCAA supplement group (n = 10), and BCAA+FO supplement group (n = 10). The BCAA+FO group consumed eicosapentaenoic acid (EPA) 600 mg and docosahexaenoic acid (DHA) 260 mg per day for 8 weeks, while the BCAA and BCAA+FO groups consumed 9.6 g per day for 3 days prior to and until 5 days after ECCs. Participants performed six sets of 10 ECCs at 100% maximal voluntary contraction (MVC) using dumbbells. Changes in MVC torque, range of motion (ROM), muscle soreness using visual analog scales, upper circumference, muscle thickness, echo intensity, and serum creatine kinase (CK) were assessed before, immediately after, and 1, 2, 3, and 5 days after ECCs.ResultsThe MVC torque was significantly higher in the BCAA+FO group than in the PL group immediately after ECCs (p < 0.05) but not in the BCAA group. Both BCAA and BCAA+FO groups showed greater ROM and lower muscle soreness than the PL group (p < 0.05). CK was significantly lower in the BCAA group than in the PL group at 5 days after ECCs (p < 0.05).ConclusionsThis study reveals that supplementation with BCAA and FO may favorably impact immediate recovery of peak torque production. Alternatively, in comparison to PL group, BCAA supplementation favorably reduces creatine kinase.