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Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study.
Woo, SL, Yang, J, Hsu, M, Yang, A, Zhang, L, Lee, RP, Gilbuena, I, Thames, G, Huang, J, Rasmussen, A, et al
The American journal of clinical nutrition. 2019;(6):1569-1577
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Abstract
BACKGROUND Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism. OBJECTIVES The aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals. METHODS This is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers. RESULTS BCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA -3.3% ± 3%; low-BCAA: 10.0% ± 6%; P = 0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9% ± 8%; low-BCAA: 14.8% ± 10%; P = 0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0 ± 1 pg/mL; low-BCAA: 5.7 ± 1 pg/mL; P = 0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4% ± 9%; low-BCAA: 29.0% ± 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4% ± 187%; low-BCAA: 20.6% ± 33%; P = 0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% ± 12%; low-BCAA: 9.2% ± 11%), valine (BCAA: 9.1% ± 11%; low-BCAA: 12.0% ± 13%), or isoleucine (BCAA: 2.5% ± 11%; low-BCAA: 7.3% ± 11%). CONCLUSIONS Our data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.
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Aqueous Humor Analysis Identifies Higher Branched Chain Amino Acid Metabolism as a Marker for Human Leukocyte Antigen-B27 Acute Anterior Uveitis and Disease Activity.
Verhagen, FH, Stigter, ECA, Pras-Raves, ML, Burgering, BMT, Imhof, SM, Radstake, TRDJ, de Boer, JH, Kuiper, JJW
American journal of ophthalmology. 2019;:97-110
Abstract
PURPOSE Human leukocyte antigen-B27 (HLA-B27)-positive acute anterior uveitis (AAU) has a higher recurrence rate and shows more anterior chamber cell infiltration compared with HLA-B27-negative patients, suggesting distinct etiologies of these clinically overlapping conditions. To advance our understanding of the biology of AAU, we characterized the metabolic profile of aqueous humor (AqH) of patients with HLA-B27-associated AAU (B27-AAU) and noninfectious idiopathic AAU (idiopathic AAU). DESIGN Experimental laboratory study. METHODS AqH samples from 2 independent cohorts totaling 30 patients with B27-AAU, 16 patients with idiopathic AAU, and 20 patients with cataracts underwent 2 individual rounds of direct infusion mass spectrometry. Features predicted by direct infusion mass spectrometry that facilitated maximum separation between the disease groups in regression models were validated by liquid chromatography/tandem mass spectrometry-based quantification with appropriate standards. RESULTS Partial least square-discriminant analysis revealed metabolite profiles that were able to separate patients with B27-AAU from those with iodiopathic AAU. Pathway enrichment analysis, based on metabolites on which separation of the groups in the partial least square-discriminant analysis model was based, demonstrated the involvement of branched-chain amino acid biosynthesis, ascorbate and aldarate metabolism, the tricarboxylic acid cycle, and glycolysis-diverting pathways (eg, serine biosynthesis) across all investigated cohorts. Notably, the metabolite ketoleucine was elevated in B27-AAU across all 3 runs and moderately-but robustly-correlated with anterior chamber cell count (correlation coefficient range 0.41-0.81). CONCLUSIONS These results illustrate metabolic heterogeneity between HLA-B27-positive and HLA-B27-negative AAU, including an increase of branched-chain amino acid biosynthesis, that reflects disease activity in AAU.
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The Effects of Omega-3 and Branched-Chain Amino Acids Supplementation on Serum Apoptosis Markers Following Acute Resistance Exercise in Old Men.
Sheikholeslami-Vatani, D, Ahmadi, S, Faraji, H
Journal of aging and physical activity. 2019;(2):198-204
Abstract
The potential benefits of omega-3 fatty acids and branched-chain amino acids (BCAAs) supplements on exercise-induced apoptosis are not clear. In a crossover randomized study, 11 men (age = 62.8 ± 2.2 years) performed an acute bout of resistance exercise and underwent 1-week supplementation with either 20 g of BCAA or 2,700 mg of omega-3/day. Subjects performed the same exercise after supplementation protocols. Following a 3-week washout period, subjects switched groups. Circulating levels of soluble Fas ligand (sFasL), cytochrome c, Bax, Bcl-2, and nuclear factor-kappa B were measured before and immediately after exercise sessions. sFasL, cytochrome c, and Bax increased after exercise. Simple main effect of time on sFasl was significant in control trial but not in omega-3 and BCAA trials. There were no differences in nuclear factor-kappa B and Bcl-2 between control and supplement trials. This study showed that adding omega-3 fatty acids or BCAA to the dietary regime of old men could partially attenuate resistance exercise-induced apoptosis.
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[The efficiency of branched chain aminoacids (BCAA) in the nutrition of combat sport athletes].
Trushina, EN, Vybornov, VD, Riger, NA, Mustafina, OK, Solntsevа, TN, Timonin, AN, Zilova, IS, Radzhabkadiev, RM
Voprosy pitaniia. 2019;(4):48-56
Abstract
Balanced nutrition of athletes involves the usage of both ordinary products and complexes of functional food ingredients that contribute to improving the performance of athletes, strengthening the immune system. One of the main components of specialized foods that are widely used in sports' nutrition and food supplements are branched chain aminoacids (BCAA): valine, leucine, isoleucine. The aim of the work was to study the effect of the BCAA intake on the parameters of body composition and the immune status of combat sport athletes during the training period. Material and methods. The object of the study was 20 athletes (masters of sports and candidates for masters of sports in combat sports: sambo, judo) at the age of 17-18 years. Athletes were distributed into 2 groups. Athletes of the main group (n=10) for 4 weeks in addition to the main diet were supplemented with BCAA at a dosage of 5 g per day. The athletes of the control group (n=10) received the main diet without BCAA inclusion. Examination of athletes of both groups was carried out at the beginning of the research and after 4 weeks of the observation period. The actual nutrition of athletes and daily energy consumption have been studied, body composition, the quantitative composition of subpopulations of peripheral blood lymphocytes, cytokine profile and hematological parameters have been determined. Results and discussion. As a result of a comprehensive survey of athletes, the positive effect of BCAA intake on the phase angle value (7.35±0.28 vs 6.41±0.32 at the beginning of the study, p<0.05) and muscle mass (25.1±0.8 vs 23.4±0.6 kg, p<0.10) has been demonstrated. In the control group these parameters did not change statistically significantly (7.05±0.25 vs 6.78±0.42 and 24.1±1.7 vs 23.8±1.5 kg). The athletes of the main group showed an increase in erythrocyte hemoglobin content (30.0±0.3 vs 29.0±0.2 pg, p<0.05). The relative content of basophilic leukocytes in athletes of the main group decreased by the end of the observation period - from 0.69±0.05 to 0.54±0.05% (p<0.05), that indicated an increase of immune resistance. The biomarker of the immunotropic effect of BCAA was the suppression of IL-4 production (1.6±0.1 to 1.3±0.1 pg/ml, p<0.05) synthesized by Th2 lymphocytes, with switching response to cellular immunity. Conclusion. The results of this study provide evidence of the effectiveness of BCAA usage in sports' nutrition for maintaining sport performance, immunity, and the adaptive potential of combat sport athletes.
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Supplementation with Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study.
Vidot, H, Cvejic, E, Finegan, LJ, Shores, EA, Bowen, DG, Strasser, SI, McCaughan, GW, Carey, S, Allman-Farinelli, M, Shackel, NA
Nutrients. 2019;(8)
Abstract
INTRODUCTION Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE. METHODS Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses. RESULTS Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels. CONCLUSION To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.
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Circulating Leptin and Branched Chain Amino Acids-Correlation with Intraductal Papillary Mucinous Neoplasm Dysplastic Grade.
Yip-Schneider, MT, Simpson, R, Carr, RA, Wu, H, Fan, H, Liu, Z, Korc, M, Zhang, J, Schmidt, CM
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2019;(5):966-974
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Abstract
BACKGROUND The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN. METHODS Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology. RESULTS Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed. CONCLUSIONS Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.
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The Effect of Branched Chain Amino Acids-Enriched Nutritional Supplements on Activities of Daily Living and Muscle Mass in Inpatients with Gait Impairments: A Randomized Controlled Trial.
Moriwaki, M, Wakabayashi, H, Sakata, K, Domen, K
The journal of nutrition, health & aging. 2019;(4):348-353
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Abstract
OBJECTIVE To investigate the effects of continuous intervention with branched chain amino acids-enriched nutritional supplements from the acute phase to convalescent rehabilitation wards in inpatients with gait impairments. DESIGN Open-label, randomized, parallel-group comparison study (UMIN Clinical Trials Registry ID: UMIN000018640). SETTING Acute care and convalescent rehabilitation wards. PARTICIPANTS We studied 80 patients undergoing stand/gait training. INTERVENTIONS Participants in the intervention group (RJ group) received nutritional supplements (jelly foods comprising 2500 mg BCAA and 20 IU vitamin D) twice a day until hospital discharge. MEASUREMENTS The primary outcome was the motor components of the Functional Independence Measure (FIM-m), and the secondary outcome was skeletal muscle mass index. RESULTS Analyses were conducted on 55 patients who were able to perform stand/gait training continuously from the acute until the recovery phases. FIM-m was significantly elevated in the RJ group and the control group , but no difference was noted between the two groups. Only the RJ group showed a significant increase in skeletal muscle mass index, and the amount of variation was significantly different between the two groups (the control group decreased an average of 2.2% and the RJ group increased an average of 4.3%; P = 0.014). A significant decrease in body weight was found only in the control group (P = 0.084). CONCLUSIONS Nutritional interventions using branched chain amino acids (BCAA)-enriched nutritional supplements demonstrated no significant difference in activities of daily living; however, an increase in skeletal muscle mass was noted. Skeletal muscle mass and body weight differed significantly between the two groups, and BCAA-enriched nutritional supplements intake in acute and convalescent rehabilitation wards may be effective for the prevention of malnutrition and sarcopenia.
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Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial.
Karusheva, Y, Koessler, T, Strassburger, K, Markgraf, D, Mastrototaro, L, Jelenik, T, Simon, MC, Pesta, D, Zaharia, OP, Bódis, K, et al
The American journal of clinical nutrition. 2019;(5):1098-1107
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BACKGROUND Epidemiological studies have shown that increased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2 diabetes (T2D). This may result from altered energy metabolism or dietary habits. OBJECTIVE We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity. METHODS This randomized, placebo-controlled, double-blinded, crossover trial examined well-controlled T2D patients receiving isocaloric diets (protein: 1 g/kg body weight) for 4 wk. Protein requirements were covered by commercially available food supplemented ≤60% by an AA mixture either containing all AAs or lacking BCAAs. The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake. The patients underwent the mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), and skeletal muscle and white adipose tissue biopsies to assess insulin signaling. RESULTS After the BCAA- diet, BCAAs were reduced by 17% during fasting (P < 0.001), by 13% during HEC (P < 0.01), and by 62% during the MMT (P < 0.001). Under clamp conditions, whole-body and hepatic insulin sensitivity did not differ between diets. After the BCAA- diet, however, the oral glucose sensitivity index was 24% (P < 0.01) and circulating fibroblast-growth factor 21 was 21% higher (P < 0.05), whereas meal-derived insulin secretion was 28% lower (P < 0.05). Adipose tissue expression of the mechanistic target of rapamycin was 13% lower, whereas the mitochondrial respiratory control ratio was 1.7-fold higher (both P < 0.05). The fecal microbiome was enriched in Bacteroidetes but depleted of Firmicutes. CONCLUSIONS Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and improves white adipose tissue metabolism and gut microbiome composition. Longer-term studies will be needed to evaluate the safety and metabolic efficacy in diabetes patients.This trial was registered at clinicaltrials.gov as NCT03261362.
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Branched chain amino acids: Passive biomarkers or the key to the pathogenesis of cardiometabolic diseases?
Siomkajło, M, Daroszewski, J
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2019;(9):1263-1269
Abstract
The metabolomic approach to research on lifestyle diseases has led to the discovery of new potential biomarkers of pathological conditions as well as key metabolic pathways that may become targets of therapeutic intervention. Current evidence supports plasma branched chain amino acids (BCAAs) as potential diagnostic and prognostic biomarkers of cardiometabolic diseases. However, the biological mechanisms of the associations that have been identified are still not completely understood and should be clarified before implementing BCAA-based biomarkers in the clinical setting. The most crucial issue that needs to be solved first is determining whether BCAA plasma profile disturbances are only passive biomarkers or whether they facilitate dysmetabolic processes. In this context, further research is also warranted to investigate the role of dietary BCAAs. Gaining this knowledge would be significant progress in molecular nutrition research, providing perspective for target therapeutic and prophylactic interventions. This paper provides a comprehensive review of the main hypotheses and mechanistic models that consider circulating BCAAs both as passive biomarkers and as contributors to cardiometabolic diseases.
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The Effects of Leucine-Enriched Branched-Chain Amino Acid Supplementation on Recovery After High-Intensity Resistance Exercise.
Osmond, AD, Directo, DJ, Elam, ML, Juache, G, Kreipke, VC, Saralegui, DE, Wildman, R, Wong, M, Jo, E
International journal of sports physiology and performance. 2019;(8):1081-1088
Abstract
CONTEXT Of the 3 branched-chain amino acids (BCAA), leucine has arguably received the most attribution for the role of BCAA supplementation in alleviating symptoms of exercise-induced muscle damage and facilitation of acute performance recovery. PURPOSE To examine whether enrichment of a standard BCAA supplement with additional leucine or a standalone leucine (LEU) supplement differentially affects exercise-induced muscle damage and performance recovery compared with a standard BCAA supplement. METHODS A total of 22 recreationally active male and female subjects were recruited and assigned to consume a BCAA, leucine-enriched BCAA (LBCAA), or LEU supplement for 11 d. On the eighth day, subjects performed eccentric-based resistance exercise (ECRE). Lower-body mean average and peak power, plasma creatine kinase, soreness, and pain threshold were measured before and 24, 48, and 72 h after ECRE. RESULTS LEU showed decreased mean average power (P = .02) and mean peak power (P = .01) from baseline to 48 h post-ECRE, whereas LBCAA and BCAA only trended toward a reduction at 24 hours post-ECRE. At 48 h post-ECRE, BCAA showed greater recovery of mean peak power than LEU (P = .04). At 24 h post-ECRE, LEU demonstrated a greater increase in plasma creatine kinase from baseline than BCAA (P = .04). Area under the curve for creatine kinase was greater in LEU than BCAA (P = .02), whereas BCAA and LBCAA did not differ. Only LEU demonstrated increased soreness during rest and under muscular tension at 24 and 48 h post-ECRE (P < .05). CONCLUSIONS LBCAA failed to afford any advantages over a standard BCAA supplement for postexercise muscle recovery, whereas a LEU supplement was comparatively ineffective.