BCAA (Branched-Chain Amino Acids)

The present study aimed to investigate the association of dietary branched-chain amino acids (BCAAs) and its components with cancer, cancer mortality, and all-cause mortality in a meta-analysis of observational studies. A comprehensive search was conducted between electronic databases (PubMed, Scopus, and Web of Science) until September 2022. Odds ratios (OR), hazard ratios (HR), and relative risks (RR) were extracted. Eight articles (six studies on breast cancer (BC) and digestive cancers risk, and three studies on both BC and digestive cancers mortality, and all-cause mortality) were included. The present study showed no statistically significant association between dietary BCAAs and its components with BC and digestive cancers (RRBCAA: 0.87, 95% CI: 0.68-1.10, RRLeucine: 0.74, 95% CI: 0.52-1.04, RRIsoleucine: 0.98, 95% CI: 0.93-1.04, RRValine: 0.76, 95% CI: 0.55-1.05). Also, no statistically significant relationship between dietary BCAAs and its components with both BC and digestive cancers mortality (RRBCAA: 0.95, 95% CI: 0.68-1.33, RRLeucine: 0.95, 95% CI: 0.79-1.15, RRIsoleucine: 0.95, 95% CI: 0.79-1.14, RRValine: 1.01, 95% CI: 0.84-1.21) and all-cause mortality (RRBCAA: 0.98, 95% CI: 0.73-1.32, RRLeucine: 1.02, 95% CI: 0.81-1.29, RRIsoleucine: 0.96, 95% CI: 0.73-1.27, RRValine: 1.02, 95% CI: 0.79-1.32) were observed. Our findings showed no significant association between dietary BCAAs and its components with BC and digestive cancers, BC and digestive cancers mortality, and all-cause mortality.

Recently, the serum levels of branched-chain amino acids (BCAAs) have been considered as an indicator to evaluate health status and predict chronic diseases risk. This systematic review and meta-analysis aimed to assess the relationship between Serum BCAAs and the risk of all-cause mortality. We carried out a comprehensive and systematic search in various important databases, including PubMed, Scopus, and Web of Science databases to find the relevant studies published up to October 2022 with no language, design, or time limitation. We extracted the reported hazard ratio (HR) with 95% confidence interval (CI) and odds ratio (OR) with 95%CI in cohorts and case-control studies, respectively, and computed the log HR or OR and its standard error. Then, we used the random-effects model with inverse variance weighting method for the present meta-analysis, to calculate the pooled effect size. Ten observational studies, including nine cohort studies and one case-control study, were included in the present meta-analysis. The number of participants ranges from 53 to 26,711, with an age range of 18-99 years. During 6 months to 24 years of follow-up, 3599 deaths were ascertained. The pooled results indicated that there was no significant association between serum BCAAs (RR: 1.17; 95% CI 0.85-1.60), isoleucine (RR: 1.41; 95%CI 0.92-2.17), leucine (RR: 1.13; 95% CI 0.94-1.36), and valine (RR: 1.02; 95%CI 0.86-1.22) and all-cause mortality. Also, there was significant heterogeneity between studies for serum BCAAs (I2 = 74.1% and P-heterogeneity = 0.021), isoleucine (I2 = 89.4% and P-heterogeneity < 0.001), leucine (I2 = 87.8% and P-heterogeneity < 0.001), and valine (I2 = 86.6% and P-heterogeneity < 0.001). Our results suggested that the serum BCAAs and its components, including isoleucine, leucine, and valine, were not associated with the risk of all-cause mortality. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Mild traumatic brain injury (mTBI) represents a significant burden for individuals, economies, and healthcare systems worldwide. Recovery protocols focus on medication and physiotherapy-based interventions. Animal studies have shown that antioxidants, branched-chain amino acids and omega-3 fatty acids may improve neurophysiological outcomes after TBI. However, there appears to be a paucity of nutritional interventions in humans with chronic (≥1 month) symptomology post-mTBI. This systematic literature review aimed to consolidate evidence for nutrition and dietary-related interventions in humans with chronic mTBI. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021277780) and conducted following the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three reviewers searched five databases (PubMed/MEDLINE, Web of Science, SPORTDiscus, CINAHL Complete and Cochrane), which yielded 6164 studies. Nine studies met the inclusion criteria. The main finding was the lack of interventions conducted to date, and a quality assessment of the included studies was found to be fair to good. Due to heterogeneity, a meta-analysis was not feasible. The six nutrition areas identified (omega-3 fatty acids, melatonin, Enzogenol®, MLC901, ketogenic diet and phytocannabinoids) were safe and well-tolerated. It was found that these nutritional interventions may improve cognitive failures, sleep disturbances, anxiety, physical disability, systolic blood pressure volume and sport concussion assessment tool scores following mTBI. Potential areas of improvement identified for future studies included blinding, reporting compliance, and controlling for confounders. In conclusion, further research of higher quality is needed to investigate the role of nutrition in recovery from mTBI to reduce the burden of chronic outcomes following mTBI.

Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored. Methods: A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Health and Care Excellence (NICE) website. The data sources included EMBASE, MEDLINE and PubMed for all papers from inception until November 2021. Nine studies were identified in this systematic review and meta-analysis. Stratification was based on follow-up times (0−6, 6−12 and 12 or more years) and controlling of body mass index (BMI) through the specific assessment of overweight cohorts was also undertaken. Results: The meta-analysis revealed a statistically significant positive association between BCAA concentrations and the development of T2DM, with valine OR = 2.08 (95% CI = 2.04−2.12, p < 0.00001), leucine OR = 2.25 (95% CI = 1.76−2.87, p < 0.00001) and isoleucine OR = 2.12, 95% CI = 2.00−2.25, p < 0.00001. In addition, we demonstrated a positive consistent temporal association between circulating BCAA levels and the risk of developing T2DM with differentials in the respective follow-up times of 0−6 years, 6−12 years and ≥12 years follow-up for valine (OR = 2.08, 1.86 and 2.14, p < 0.05 each), leucine (OR = 2.10, 2.25 and 2.16, p < 0.05 each) and isoleucine (OR = 2.12, 1.90 and 2.16, p < 0.05 each) demonstrated. Conclusion: Plasma BCAA concentrations are associated with T2DM incidence across all temporal subgroups. We suggest the potential utility of BCAAs as an early biomarker for T2DM irrespective of follow-up time.

This systematic review aimed to examine the health outcomes and environmental impact of edible insect consumption. Following PRISMA-P guidelines, PubMed, Medline ProQuest, and Cochrane Library databases were searched until February 2021. Twenty-five articles met inclusion criteria: twelve animal and six human studies (randomized, non-randomized, and crossover control trials), and seven studies on sustainability outcomes. In animal studies, a supplement (in powdered form) of 0.5 g/kg of glycosaminoglycans significantly reduced abdominal and epididymal fat weight (5-40% and 5-24%, respectively), blood glucose (10-22%), and total cholesterol levels (9-10%), and a supplement of 5 mg/kg chitin/chitosan reduced body weight (1-4%) and abdominal fat accumulation (4%) versus control diets. In other animal studies, doses up to 7-15% of edible insect inclusion level significantly improved the live weight (9-33%), reduced levels of triglycerides (44%), cholesterol (14%), and blood glucose (8%), and increased microbiota diversity (2%) versus control diet. In human studies, doses up to 7% of edible insect inclusion level produced a significant improvement in gut health (6%) and reduction in systemic inflammation (2%) versus control diets and a significant increase in blood concentrations of essential and branched-chain amino acids and slowing of digestion (40%) versus whey treatment. Environmental indicators (land use, water footprint, and greenhouse gas emissions) were 40-60% lower for the feed and food of edible insects than for traditional animal livestock. More research is warranted on the edible insect dose responsible for health effects and on environmental indicators of edible insects for human nutrition. This research demonstrates how edible insects can be an alternative protein source not only to improve human and animal nutrition but also to exert positive effects on planetary health.

Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.

The global population is living longer; however, not everyone ages at the same rate with regard to their physical and cognitive abilities and their vulnerability to certain diseases and death. This review aimed to synthesize the contribution of biological age-predictive biomarkers to nutrition research and highlight the implications for future research and clinical practice. MEDLINE, CINAHL, and Cochrane CENTRAL were systematically searched on 30 September 2021 for randomized controlled trials and cross-sectional studies examining the association between nutrition and biological age in older adults reporting on genetic, clinical, or molecular biomarkers of biological aging. Cochrane's ROB 2 and ROBINS-I were used to assess the quality of included studies. Synthesis was undertaken narratively. Of 1245 records identified from the search, 13 studies from 8 countries and territories, involving 5043 participants, were included. Seven studies assessed associations between nutrient food intake and telomere attrition, reporting protective effects for branched-chain amino acids, calcium and vitamin D, and a diet of a lower inflammatory index; whereas they found shorter telomeres in people consuming more processed foods and arachidonic acid and other proinflammatory compounds. Five studies examined the associations between plasma nutrition biomarkers and cognitive function, and found a protective effect for HDL cholesterol, lycopene, carotenoids, ω-3 and ω-6 fatty acids, and vitamins B, C, D, and E; whereas trans fatty acids and fibrinogen correlated with a decline in cognitive function. One study used Horvath's clock and reported the epigenetic rejuvenation effect of a Mediterranean diet. In conclusion, biological aging was negatively associated with an anti-inflammatory diet. However, a few studies did not control for the confounding effect of other lifestyle factors. Future research should address this and also assess the synergistic effect of different nutrients, their combinations, and evaluate their dose-response relations. Nutrition practice can incorporate updated screening procedures for older people that include relevant biological aging nutrition markers, leadi

IMPORTANCE: Multiple nutritional therapies are currently available for patients with liver cirrhosis, yet many interventions have not been compared head-to-head within randomized clinical trials. OBJECTIVE: To evaluate the improvement of nutritional indicators and liver function indexes of liver cirrhosis treated with different nutrition intervention. DATA SOURCE: We searched PubMed, Embase. com and Cochrane Library database from construction to April 3, 2020. After eliminating the duplicated or overlapping reports, 6 studies were included. We performed a Bayesian network meta-analysis by Stata 12.0 and GeMTC 0.14.3 in order to compare different nutritional interventions with consistency model. STUDY SELECTION: Randomized clinical trials comparing 2 or more therapies in patients with cirrhosis were evaluated. Six randomized clinical trials met the selection criteria. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed the full manuscripts of eligible studies and extracted information into an electronic database: patients' characteristics study design, interventions, the number of events of interest in each group. MAIN OUTCOMES AND MEASURES: Body mass index, Child-Pugh score, model for end-stage liver disease score, total bilirubin, alanine transaminase, aspartate transaminase, total protein, Triceps skinfold, Midarm Muscle Circumference, Fischer ratio, overall survival. RESULTS: There are 6 studies enrolling a total of 1148 patients who received different nutrition supports including parenteral nutrition (PN), enteral nutrition (EN), EN (without branched-chain amino acids), EN + intestinal probiotics, PN + EN, late evening snacks (LES), EN + LES, noLES. The direct comparisons showed that the effect of EN was better than EN (without branched-chain amino acids); EN + intestinal probiotics was better than EN and PN; PN + EN was better than them alone; EN + LES was better than LES and EN; LES was better than noLES. Although the difference of indirect comparisons between the included regimens was not statistically significant, the results showed that EN + intestinal probiotics appeared to be superior to PN + EN. While LES and EN + LES seemed to ra

PURPOSE: According to criteria recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), we analyzed the effects of branched-chain amino acid (BCAA)-rich supplements on muscle strength, muscle mass, and physical performance in older people. METHODS: We searched PubMed, Embase, Cochrane Library, and CINAHL from inception until March 2021. Randomized controlled trials that examined the effect of BCAA-rich supplements on older people were included. Random-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were stratified by participant and supplementation characteristics. Meta-regression analyses were performed to examine the effect of continuous variables. RESULTS: Thirty-five studies were included in this meta-analysis. Quality assessment revealed that 14 of 35 RCTs had some potential bias. The overall standardized mean difference (SMD) in muscle strength, muscle mass, and physical performance between the supplement and control groups was 0.35 (95% CI = [0.15, 0.55], P = 0.0007), 0.25 (95% CI = [0.10, 0.40], P = 0.0008), and 0.29 (95% CI = [0.00, 0.57], P = 0.05), respectively. Subgroup analysis revealed that essential amino acid supplementation improved handgrip strength more significantly than whey protein supplementation in older people. Meta-regression analysis revealed a significant linear relationship between improvements in handgrip strength and body mass index. CONCLUSIONS: BCAA-rich supplementation by older people may have beneficial effects on muscle mass and strength. However, the included studies had high heterogeneity, and the results must be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42020206674. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

BACKGROUND: Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer's ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery. METHODS: MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies' quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate. RESULTS: 20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = -2.07 days; 95% CI = -3.97 to -0.17; P = .03; k = 5; N = 362; I2 = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were ident

The GG genotype of the Patatin-like phosphatase domain-containing 3 (PNPLA3), dietary fat, short-chain fatty acids (SCFA) and branched-chain amino acids (BCAA) are linked with non-alcoholic fatty liver disease. We studied the impact of the quality of dietary fat on plasma (p) and fecal (f) SCFA and p-BCAA in men homozygous for the PNPLA3 rs738409 variant (I148M). Eighty-eight randomly assigned men (age 67.8 ± 4.3 years, body mass index 27.1 ± 2.5 kg/m2) participated in a 12-week diet intervention. The recommended diet (RD) group followed the National and Nordic nutrition recommendations for fat intake. The average diet (AD) group followed the average fat intake in Finland. The intervention resulted in a decrease in total p-SCFAs and iso-butyric acid in the RD group (p = 0.041 and p = 0.002). Valeric acid (p-VA) increased in participants with the GG genotype regardless of the diet (RD, 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.005 and AD, 3.8 ± 0.3 to 9.7 ± 8.5 µmol/g, p = 0.015). Also, genotype relation to p-VA was seen statistically significantly in the RD group (CC: 3.7 ± 0.4 to 4.2 ± 1.7 µmol/g and GG: 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.0026 for time and p = 0.004 for time and genotype). P-VA, unlike any other SCFA, correlated positively with plasma gamma-glutamyl transferase (r = 0.240, p = 0.025). Total p-BCAAs concentration changed in the AD group comparing PNPLA3 CC and GG genotypes (CC: 612 ± 184 to 532 ± 149 µmol/g and GG: 587 ± 182 to 590 ± 130 µmol/g, p = 0.015 for time). Valine decreased in the RD group (p = 0.009), and leucine decreased in the AD group (p = 0.043). RD decreased total fecal SCFA, acetic acid (f-AA), and butyric acid (f-BA) in those with CC genotype (p = 0.006, 0.013 and 0.005, respectively). Our results suggest that the PNPLA3 genotype modifies the effect of dietary fat modification for p-VA, total f-SCFA, f-AA and f-BA, and total p-BCAA.

Exercise affects serum levels of amino acids and their metabolites, with important metabolic consequences. Since vitamin D impacts skeletal muscle protein degradation, we hypothesised that it would also impact exercise-induced changes in serum amino acid levels and the serum levels of arginine metabolites, influencing the body's ability to synthesise NO. Accordingly, we analysed the effect of a single high-dose vitamin D supplementation on the serum levels of various amino acids in ultramarathon runners. Thirty-five male amateur runners were assigned to the supplemented group, administered 150,000 IU vitamin D in vegetable oil 24 h before the run (n = 16), or the control (placebo) group (n = 19). Blood was sampled 24 h before, immediately after, and 24 h after the run. Changes in the serum levels of some amino acids were distinct in the two groups. The asymmetric dimethyl arginine levels were significantly decreased immediately after the run and increased 24 h later and were not affected by the supplementation. The symmetric dimethyl arginine levels were increased after the run in both groups but were lower in the supplemented group than in the placebo group 24 h after the run. The dimethylamine levels increased significantly in the supplemented group as compared to the placebo group. In conclusion, vitamin D impacts exercise-induced changes in serum amino acids and methylated arginine metabolites.

BACKGROUND: Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance. METHODS: In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period. RESULTS: There was a significant increase (p = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase (p = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test. CONCLUSIONS: The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower

BACKGROUND CONTEXT: Adequate 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. PURPOSE: To 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/SETTING: A single-center, single-blind randomized controlled trial. PATIENT SAMPLE: Eighty patients who received lumbar surgery for LSS. OUTCOME MEASURES: The 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. METHODS: Patients 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. RESULTS: No 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. CONCLUSIONS: BCAA 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 developmen

SCOPE: Adequate intake of whole grain foods is beneficial to type 2 diabetes mellitus (T2DM). Whether the preventive effects are related with metabolism of branched-chain amino acids (BCAAs) is unclear. The study aims to evaluate the effects of germinated brown rice (GBR) intervention on BCAAs metabolism in T2DM patients. METHODS AND RESULTS: In this randomized controlled trial, subjects with T2DM are instructed to consume 100 g day-1 GBR (GBR group, n=42) or equal staple food (Control group, n=25) for 3 months. Food frequency questionnaires (FFQ) and serum samples are collected before and after the intervention. In the GBR group, fasting blood glucose (FBG), fasting insulin (FINS), and serum BCAAs are decreased, and islet function is improved (p<0.05). Logistic regression analysis showed that FBG (odds ratios [OR]: 1.55, 95% confidence interval [CI]: 1.01-1.84) and energy (OR: 1.21, 95% CI: 1.09-1.30) are positively associated with serum total BCAAs level, while FINS is negatively associated (OR: 0.20, 95% CI: 0.04-0.88). Simultaneously, the key enzymes of BCAAs decomposition, which promotes glycolysis by activating pyruvate dehydrogenase (PDH), are significantly increased. CONCLUSION: GBR improves the indicators of T2DM patients, and the underlying mechanisms include improving insulin resistance and accelerating catabolism of BCAAs. © 2023 Wiley-VCH GmbH.

The study investigates the effects of wheat biscuits supplemented with plant flours originating from legumes/seeds enriched either in L-arginine (L-arg) or branched-chain amino acids (BCAAs) on postprandial glucose response of healthy subjects. Gastrointestinal hormone and amino acid responses as well as subjective appetite sensations are also evaluated. Subjects consumed wheat-based biscuits, enriched either in L-arg (ArgB) or BCAAs (BCAAsB) or a conventional wheat biscuit (CB) or a glucose solution (GS) in an acute randomized crossover design. Responses of glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and glicentin, as well as those of L-arginine, L-leucine, L-isoleucine and L-valine, were evaluated over 180 min. Consumption of ArgB and BCAAsB elicited lower glucose iAUC compared to GS (p < 0.05). A lower iAUC for insulin was observed after consumption of BCAAsB (p < 0.05 compared to CB and ArgB), while ArgB elicited higher iAUC for GLP-1 accompanied by higher glicentin response (p < 0.05 compared to CB). BCAAsB and ArgB increased postprandial amino acid concentrations and caused stronger satiety effects compared to CB. Increasing protein content of wheat biscuits with supplementation of plant flours originating from legumes/seeds decreases postprandial glycemia and provides with healthier snack alternatives which can easily be incorporated into diet.

BCAAs supplementation has been widely used for post-exercise recovery. However, no evidence is currently available to answer the question of whether BCAAs supplementation can attenuate muscle damage and ameliorate recovery after a bout of change of direction (COD) sprinting, which is an exercise motion frequently used during team sport actions. This study aimed to assess the effect of BCAAs supplementation on muscle damage markers, subjective muscle soreness, neuromuscular performance, and the vascular health of collegiate basketball players during a 72 h recovery period after a standardized COD protocol. Participants orally received either BCAAs (0.17 g/kg BCAAs + 0.17 g/kg glucose) or placebo (0.34 g/kg glucose) supplementation before and immediately after a COD exercise protocol in a randomized, crossover, double-blind, and placebo-controlled manner. Creatine kinase increased immediately after exercise and peaked at 24 h, muscle soreness remained elevated until 72 h, whilst arterial stiffness decreased after exercise for both supplemented conditions. A negligibly lower level of interleukin-6 was found in the BCAAs supplemented condition. In conclusion, the results of this study do not support the benefits of BCAAs supplementation on mitigating muscle damage and soreness, neuromuscular performance, and arterial stiffness after COD for basketball players.

BACKGROUND: Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. METHODS: In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. RESULTS: Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-M

SCOPE: Branched Chain Amino Acids (BCAA) plasma levels may be differentially associated with type 2 diabetes mellitus (T2DM) remission through the consumption of the Mediterranean diet (Med) and a low-fat (LF) diet. METHODS: One hundred eighty-three newly diagnosed T2DM patients within the CORDIOPREV study are randomized to consume the Med or a LF diet. BCAA plasma levels (isoleucine, leucine, and valine) are measured at fasting and after 120 min of an oral glucose tolerance test (OGTT) at the baseline of the study and after 5 years of the dietary intervention. RESULTS: Isoleucine, leucine, and valine plasma levels after 120 min of an OGTT in the Med diet (N = 80) are associated by COX analysis with T2DM remission: HR per SD (95% CI): 0.53 (0.37-0.77), 0.75 (0.52-1.08), and 0.61 (0.45-0.82), respectively; no association is found in patients who consumed a LF diet (N = 103). BCAA plasma levels combined in a score show a HR of 3.33 (1.55-7.19) of T2DM remission for patients with a high score values in the Med diet, while in those with a LF diet, no association is found. CONCLUSION: The study suggests that BCAA measurements potentially be used as a tool to select the most suitable diet to induce T2DM remission by nutritional strategies. © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.

Functional ability and intrinsic capacity are key elements of healthy aging, in which exercise and good nutrition play important roles. This 12-week double-blinded randomized controlled trial enrolled community-dwelling adults aged 50 years and older to examine the effects of Sarcojoint®, a comprehensive formula for the musculoskeletal system, plus resistance exercise on muscle mass. This study intended to enroll 80 participants with a randomly selected subsample of 32 participants (16 from the intervention group and 16 from controls) for magnetic resonance imaging (MRI) to assess the cross-sectional area of the bilateral mid-thighs. The participants were then randomly assigned to the intervention group (Sarcojoint® 1 package twice a day) and control group (vitamin B as placebo) at a 1: 1 ratio. All the participants were required to undergo a regular exercise program (45 min at the gym per week and two sessions of 30-min exercise at home). The data from 66 participants (68.1 ± 7.1 years and 16.7% males; intervention group: 32, control group: 34) were available for analysis. The whole study was pre-registered and data reporting followed Consolidated Standards of Reporting Trials with the primary endpoints of muscle mass, 30-s chair-rise test, and gait speed. Results of MRI were the subgroup analysis to examine muscle mass and intramuscular adiposity. The baseline characteristics of all the participants between groups were similar, as well as those of the MRI subgroups. Within-group comparisons showed that the intervention group, but not the control group, significantly reduced the total body fat percentage (34.3 ± 5.5 vs. 35.0 ± 5.4%, P = 0.021). Serum vitamin D was increased in the intervention group (24.1 ± 6.1 vs. 21.1 ± 7.0 ng/mL; P = 0.025) and was reduced in the control group (18.0 ± 5.2 vs. 20.2 ± 5.8 ng/mL; P = 0.006). The physical performance tests of both groups were significantly improved. The between-group analysis showed no significant differences in 30-s chair stand test, handgrip strength and appendicular muscle mass. The sub-group analysis showed significant improvement in the serum levels of vitamin D (6.70 ± 8.20 vs. -0.50 ± 3.90 ng/mL; P = 0.00

Branched-chain amino acids (BCAA) leucine, isoleucine, and valine are metabolized by complex branched-chain ketoacids dehydrogenase (BCKDH). In Maple Syrup Urine Disease (MSUD), the BCKDH complex has its activity blocked by a genetic mutation, compromising the BCAA metabolism and leading to the accumulation of these BCAA, related to neurological damage in this disease. Thus, minocycline is a broad-spectrum antibiotic, bacteriostatic, and studies have shown benefits in neurodegenerative disease progression, like reduction of oxidative stress, inflammation, and downregulation of molecular pathways, such as apoptosis. Therefore, we make the hypothesis that the minocycline can ameliorate oxidative stress in the MSUD model. For this, we used 7-day-old male rats, who were treated with BCAA (leucine 393.42 mg/kg, isoleucine 121.66 mg/kg and valine 126.4 mg/kg) or saline solution (0,9%) subcutaneously, water, or minocycline (50 mg/kg) via gavage. Our results show that the MSUD group presents an increase in DCFH oxidation and TBARS levels, as well as a decrease in sulfhydryl content, related to oxidative species production, lipid and protein damage, and minocycline treatment rescues this damage found. In antioxidant activity, we found an increase in SOD activity also, a decrease in CAT in all groups studied compared to the control group. So, our results present positive effects of minocycline in MSUD, showing a potential use in this disease; moreover, more studies are necessary to understand the role of this molecule in this disease. © 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

The gut microbiome has emerged as a key factor influencing a wide range of host physiological processes and behaviors, though the mechanisms behind these effects remain only partially understood. In this study, we explored the role of the gut microbiome in memory regulation using a parasitoid wasp-induced oviposition depression paradigm in Drosophila melanogaster. Our findings show that flies with depleted gut microbiota, either through axenic culture or antibiotic treatment, exhibited significant memory impairments. However, reintroducing the commensal bacterium Lactobacillus plantarum alone was sufficient to restore memory, while coinoculation with Acetobacter pomorum further enhanced memory performance. Hemolymph metabolomic analyses revealed reduced amino acid levels in antibiotic-treated flies, which were linked to impaired Drosophila target of rapamycin (dTOR) signaling. Additionally, genetic manipulation of dTOR or dietary supplementation with branched-chain amino acids either mimicked or rescued the memory deficits caused by antibiotic treatments. These results suggest that the gut microbiome is essential for regulating memory function by maintaining amino acid homeostasis and proper dTOR signaling, with profound implications for advancing knowledge of cognitive regulation.

BACKGROUND/OBJECTIVES: Inherited metabolic disorders (IMDs) are a group of genetic conditions affecting metabolic pathways. The treatment of some IMDs requires the dietary restriction of specific amino acids. IMDs may also necessitate the supplementation of one or more amino acids due to factors such as reduced dietary intake, impaired synthesis, defective transport or absorption, or increased utilization. This literature review aims to evaluate the most recent evidence regarding amino acid supplementation in IMDs, considering not only the prevention of amino acid deficiency and toxic accumulation but also the competition with other toxic metabolites. METHODS: A systematic search strategy was developed and applied to PubMed/Medline and Scopus databases to identify relevant studies. Amino acids were categorized into six groups: branched-chain amino acids, aromatic amino acids, sulfur amino acids, urea cycle amino acids, other essential amino acids, and other non-essential amino acids. RESULTS: A total of 24 rare IMDs were evaluated. A final number of 99 selected articles were assessed based on the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. Although this work represents a preliminary non-systematic review, it highlights the need for further studies and data collection. CONCLUSIONS: Future research must establish the plasma amino acid levels that indicate the need for supplementation, specify the appropriate dosages (g/day or mg/kg/day), determine the optimal treatment duration, and, crucially, define the target plasma ranges to be maintained for effective management of IMDs.

Numerous studies have shown that dietary factors can reduce the risk of developing gout, and changes in serum AA also affect gout risk. However, current research lacks insights into how dairy products with varying fat content influence serum AA and gout risk, as well as the mediating effects of AA. This study employed Mendelian randomization (MR) to analyze the association between 3 milk consumption phenotypes with different fat contents and gout. We found that only whole milk was associated with a reduced risk of gout, whereas no association was observed with the other 2 milk types. Subsequent mediation analysis revealed that isoleucine played a mediating role, with a mediation effect of -0.198 (95% CI: -0.354 to -0.072), accounting for 66.32% of the total effect, and the mediation effect was significant (P = 0.006). The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and β2-microglobulin (β2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, β2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, β2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological

BACKGROUND: Increased waist/hip ratio (WHR) contributes to type 2 diabetes, fatty liver, dyslipidaemia, hypertension and coronary artery disease, with potential sex-differential effects. Postulated mediators include increased lipid flux, branched-chain amino acids, glycine and glycoprotein acetyl, but their relative contributions and sex-specific impact on WHR-associated cardiometabolic disease (CMD) are not established. METHODS: We therefore undertook combined and sex-stratified Mendelian randomization (MR) to assess the relative causal contributions of these mediators to WHR-associated CMD using summary statistics from the largest genome-wide association studies in European ancestries. RESULTS: In sex-combined MR analyses, increased WHR significantly reduces high-density lipoprotein (beta = -0.416, SE = 0.029, p = 2.87E-47), increases triglyceride (beta = 0.431, SE = 0.029, p = 1.87E-50), type 2 diabetes (odds ratio = 2.747, SE = 0.09, p = 26E-23), coronary artery disease (odds ratio = 1.478, SE = 0.045, p = 6.96E-18), alanine transaminase (beta = 0.062, SE = 0.004, p = 6.88E-67), and systolic (beta = 0.134, SE = 0.022, p = 7.81E-10) and diastolic blood pressure (beta = 0.162, SE = 0.026, p = 5.38E-10). Adjustment for the mediators attenuated WHR's effects, but the associations remained significant with concordant results in females. In males, a similar pattern was seen, except after adjusting for the effect of the ratio of monounsaturated fatty acid to total free fatty acid, the potential causal effect of WHR was no longer significant: high-density lipoprotein (beta = -0.117, SE = 0.069, p = .09) and triglyceride (beta = 0.051, SE = 0.068, p = .459). CONCLUSIONS: MR suggests WHR increases the risk of CMD independent of these mediators, with the exception of dyslipidaemia in males, which is largely driven by the monounsaturated fatty acid to total free fatty acid ratio. © 2024 John Wiley & Sons Ltd.

OBJECTIVE: This study aimed to investigate the relationship between dietary branched-chain amino acids (BCAAs) and the risk of developing hypertension. METHODS: A cohort study of 14,883 Chinese adults without hypertension at baseline with were followed for an average of 8.9 years. Dietary intakes of BCAAs, including Ile, Leu, and Val, were collected using 3-day 24-h meal recall and household condiment weighing. Cox proportional hazards regression, restricted cubic splines, interaction analysis, and sensitivity analysis were used to assess the relationship between dietary BCAAs and risk of developing self-reported hypertension, adjusting for age, gender, region, body mass index (BMI), smoking and drinking status, physical activity, energy intake, salt intake. RESULTS: Among 14,883 study subjects, 6386(42.9%) subjects aged ≥ 45 years at baseline, 2692 (18.1%) had new-onset hypertension during the study period, with a median age of 56 years. High levels of dietary BCAAs were associated with an increased risk of new-onset hypertension. Compared with the 41st-60th percentile, multivariable adjusted hazard ratio (HR) for new-onset hypertension was 1.16 (95% CI 1.01-1.32) for dietary BCAAs 61st-80th percentiles, 1.30 (1.13-1.50) for 81st-95th, 1.60 (1.32-1.95) for 96th-100th. The cut-off value of new-onset hypertension risk, total BCAAs, Ile, Leu, and Val were 15.7 g/day, 4.1 g/day, 6.9 g/day, 4.6 g/day, respectively, and the proportion of the population above these intake values were 13.9%, 13.1%, 15.4%, and 14.4%, respectively. Age, BMI, and salt intake had an interactive effect on this relationship (P < 0.001). CONCLUSION: There was a significant positive association between total dietary BCAAs, Ile, Leu, Val intake and the risk of developing hypertension, after adjustment for confounders. This relationship was influenced by age, BMI, and salt intake. Further research is needed to clarify the mechanism and potential role of BCAAs in the pathogenesis of hypertension. © 2024. The Author(s).

BACKGROUND: Living donor liver transplantation (LDLT) is currently widespread due to organ shortage. Because LDLT is a high-risk surgery for the donor, donor safety becomes an important issue. In adult LDLT, right lobe grafts are usually used, posing a greater risk to the donor than a left lobe. Reports have demonstrated that branched-chain amino acids help patients recover after hepatectomy. This study aimed to evaluate the effect of Livact granule on donor safety and recovery. METHODS: From January 2016 to December 2021, LDLT was performed on 258 patients at our center. Among them, 148 were in the non-Livact group, and 110 were in the Livact group. Six of 110 patients in the Livact group stopped taking the granules due to nausea and vomiting, leaving 104 patients in the Livact group to be analyzed. Various preoperative and postoperative factors were evaluated to assess donor safety and recovery. RESULTS: In the non-Livact group, the mean donor age was 35.8; in the Livact group, it was 40. There were no differences between the 2 groups in preoperative liver function tests and no difference in future liver remnant or steatosis. There was no difference in total bilirubin level between the 2 groups at 5 days postoperatively; however, in the Livact group, the prothrombin time international normalized ratio was lower, and albumin was higher. The days taken for total bilirubin to normalize were the same in both groups, but fewer days were needed for Livact to realize an international normalized ratio. More patients in the non-Livact group were discharged with the Jackson-Pratt drain because the drainage did not decrease. CONCLUSIONS: In donor right hepatectomy patients, taking Livact granules and branched-chain amino acids helps donor recovery. For donor safety, administration of Livact granules during the perioperative period should be considered.

Ulcerative colitis is closely associated with the dysregulation of gut microbiota. There is growing evidence that natural products may improve ulcerative colitis by regulating the gut microbiota. In this research, we demonstrated that bergenin, a naturally occurring isocoumarin, significantly ameliorates colitis symptoms in dextran sulfate sodium (DSS)-induced mice. Transcriptomic analysis and Caco-2 cell assays revealed that bergenin could ameliorate ulcerative colitis by inhibiting TLR4 and regulating NF-κB and mTOR phosphorylation. 16S rRNA sequencing and metabolomics analyses revealed that bergenin could improve gut microbiota dysbiosis by decreasing branched-chain amino acid (BCAA) levels. BCAA intervention mediated the mTOR/p70S6K signaling pathway to exacerbate the symptoms of ulcerative colitis in mice. Notably, bergenin greatly decreased the symbiotic bacteria Bacteroides vulgatus (B. vulgatus), and the gavage of B. vulgatus increased BCAA concentrations and aggravated the symptoms of ulcerative colitis in mice. Our findings suggest that gut microbiota-mediated BCAA metabolism plays a vital role in the protective effect of bergenin on ulcerative colitis, providing novel insights for ulcerative colitis prevention through manipulation of the gut microbiota.

Supplements based on protein hydrolysates have been used as an effective source to access amino acids with greater bioavailability, promoting absorption to improve body composition. Five groups of young women were randomly selected. They followed a personalized eating plan that included different protein supplements (meat, vegan, branched-chain amino acids [BCAAs], whey, and control group), combined with an exercise plan, for eight weeks, aiming to assess their consumption effects combined with resistance exercise on body composition. Bioelectrical impedance before and after the treatment was conducted. The results showed that the supplementation with BCAAs presented a significant decrease (p < 0.05) on the BMI in this group (initial BMI = 19.7 kg/m2; final BMI = 19.4 kg/m2). When comparing the final measures among the groups, the BCAAs and vegan supplements caused a significant decrease in body weight (50.24 kg and 51.34 kg, respectively). The BMI of the group supplemented with meat proteins was statistically higher (22.06 kg/m2) than that the group supplemented with BCAAs (19.4 kg/m2) (p < 0.05). No significant changes were observed in the type of protein consumed to produce muscle mass in the participants after eight weeks of study under a controlled diet and anaerobic resistance exercise. Participants exhibited energy deficiencies, but their macronutrient distribution appeared normal. Following an 8-week intervention, meat and BCAAs reduced weight and BMI, although no statistical differences were observed. It is recommended to extend the treatment for a more comprehensive understanding.