Dietary Branched-chain Amino Acids Research Articles

Dietary intake of branched-chain amino acids (BCAAs), serum BCAAs, and cardiometabolic risk markers among community-dwelling adults.

To investigate the associations between dietary/serum branched-chain amino acids (BCAAs) and cardiometabolic risk markers. In a cohort of 2791 participants, diet and cardiometabolic risk markers were measured twice at baseline in overall participants and after 1-year in a subset of 423 participants. We assessed serum BCAAs at baseline and arterial stiffness after 1-year. The cross-sectional associations between dietary/serum BCAAs and cardiometabolic risk markers were analyzed using baseline measurements by linear regression, while the 1-year longitudinal association were analyzed using repeated measurements by linear mixed-effects regression. Higher BCAA intake from poultry was associated with lower triglycerides (β=-0.028, P = 0.027) and higher high-density lipoprotein cholesterol (HDL-C, β = 0.013, P = 0.006), while BCAAs in red and processed meat or fish were inversely associated with low-density lipoprotein cholesterol (β = 0.025, P = 0.001) and total cholesterol (β = 0.012, P = 0.033), respectively. BCAAs in whole grains and nuts were associated with higher HDL-C (β = 0.011, P = 0.016), and lower TG (β=-0.021, P = 0.041) and diastolic blood pressure (β=-0.003, P = 0.027). Also, BCAAs from soy or vegetables and fruits were inversely associated with arterial stiffness (β=-0.018, P = 0.047) and systolic blood pressure (β=-0.011, P = 0.003), respectively. However, BCAAs in refined grains were positively associated with triglycerides (β = 0.037, P = 0.014). Total serum BCAAs were unfavorably associated with multiple cardiometabolic risk markers (all P < 0.05). Dietary BCAAs in poultry, whole grains and nuts, soy, and vegetables and fruits may be favorably, while BCAAs in red and processed meat, fish, and refined grains were unfavorably associated with cardiometabolic health. Serum BCAAs showed a detrimental association with cardiometabolic risk markers.

The association between dietary intake of branched-chain amino acids and odds and severity of rheumatoid arthritis.

This case-control study investigated the link between dietary branched-chain amino acids (BCAAs) and the risk and severity of rheumatoid arthritis (RA). We assessed dietary BCAA intake in 95 RA patients and 190 matched controls using a food frequency questionnaire. We also assessed the disease severity using the disease activity score 28 (DAS-28), ESR, VAS, morning stiffness, and tender and swollen joints. Higher BCAA intake, expressed as a percentage of total protein, was significantly associated with increased risk of RA for total BCAAs (OR 2.14, 95% CI 1.53-3.00, P < 0.001), leucine (OR 2.40, 95% CI 1.70-3.38, P < 0.001), isoleucine (OR 2.04, 95% CI 1.46-2.85, P < 0.001), and valine (OR 1.87, 95% CI 1.35-2.59, P < 0.001). These associations remained significant even after adjusting for potential confounders (P < 0.001). However, BCAA intake did not show any significant association with RA severity in either crude or multivariate models (P > 0.05). Our findings suggest that higher dietary BCAA intake may contribute to the development of RA, but further research is needed to confirm these observations and explore the underlying mechanisms.

Branched-chain amino acid supplementation drives dynamic changes in gut microbiota without impairing glucose and lipid homeostasis at the different stages of insulin resistance in mice on a high-fat diet

ObjectiveThe potential role of dietary branched-chain amino acids on circulating branched-chain amino acid levels and their relationship with metabolic health are complex, and the literature is inconsistent. We aimed to explore the dynamic effects of branched-chain amino acid supplementation on glucose and lipid homeostasis at different stages of insulin resistance in high-fat diet–fed mice. MethodsMale C57BL/6J mice were fed with a normal chow diet, high-fat diet, or high-fat diet supplemented with 100% branched-chain amino acids for 12 or 24 wk. Metabolic parameters and gut microbiota profiling were performed at these two time points. ResultsHigh-fat diet feeding caused varying degrees of branched-chain amino acid metabolic disorders in two different stages of insulin resistance. Supplementing with branched-chain amino acids further exacerbated branched-chain amino acid accumulation in the early stage of insulin resistance (12 wk), while adding branched-chain amino acids did not further elevate branched-chain amino acid levels in the hyperglycemia and hyperinsulinemia stage (24 wk). Compared with the high-fat diet group, branched-chain amino acid supplementation did not affect body weight; liver total cholesterol and triacylglycerol levels; and serum glucose, insulin, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels as well as glucose tolerance at these two time points but triggered dynamic changes in the gut bacterial diversity and gut microbiota composition and abundance, especially in the genus associated with obesity and related metabolic disorders. ConclusionDietary branched-chain amino acid supplementation drives dynamic changes in circulating branched-chain amino acid levels and gut microbiome without subsequent effects on glucose and lipid homeostasis in high-fat diet–induced obese mice within the parameters of our study.

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.

Dietary Branched Chain Amino Acids Association with Cancer and Mortality: A Systematic Review and Meta-Analysis of Observational Studies

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.

Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson's disease after dietary supplementation with branched-chain amino acids.

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial-gut-brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson's disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography-mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Dietary branched-chain amino acids get to the heart of H3K23Pr.

Cardiac metabolism provides effects that extend beyond the transformation of energy for the heart to operate effectively. Some metabolites also function as signaling molecules and exert transcriptional changes. Heart failure is a progressive pathology in which these metabolite functions falter. In this issue of the JCI, Yang et al. describe a protective effect from a low-branched chain amino acid (BCAA) diet in a mouse model of heart failure. The findings implicate a propionylation mark on histone H3 lysine 23 (H3K23Pr), previously shown to be dependent on the BCAA isoleucine, in transcriptional control of the cardiac stress response. The result underscores the interplay between metabolism and histone acylation, highlighting targeted dietary and pharmacological intervention as a means to decelerate cardiac hypertrophy.

266 Interactive Effects of Dietary Isoleucine and Valine Ratios to Lysine in Response to Varying Leucine to Lysine Ratios on Hepatic Protein Expression in Commercial Broilers

Abstract A central composite design (CCD) study was conducted to understand the relationship among dietary branched chain amino acid (BCAA) ratios and expression of proteins related to amino acid and protein metabolism in the liver of broilers. A total of 2,592 d-old Ross 344 × 708 male broilers were randomly placed in 144 floor pens. Each pen received 1 of 15 dietary treatments in a 23 CCD with 6 center points from 20 to 35 d of age, varying in digestible ratios of isoleucine:lysine (Ile:Lys; 52 to 75), valine:lysine (Val:Lys; 64 to 87), and leucine:lysine (Leu:Lys; 110 to 185). On d 35, 1 bird per pen was selected, euthanized, and liver tissue samples were collected for protein extraction and proteomic analysis via data independent acquisition protein sequencing with a timsTOF Pro 2 LC/MS/MS and Spectronaut 15 software. Dihydrolipoamide acetyltransferase (PDHX), aspartate aminotransferase (GOT2), branched-chain-amino-acid aminotransferase (BCAT1), diphosphomevalonate decarboxylase (MVD), acylamino-acid-releasing enzyme (APEH), and aspartate aminotransferase (GOT1) were identified and quantified. Protein quantification data were analyzed as a CCD using the RSREG procedure of SAS v. 9.4 with significance declared at P ≤ 0.10. When the individual AA effect in the response surface (RS) regression analysis was P ≤ 0.2, raw protein quantification data were analyzed as a 1-way ANOVA and the PDIFF option of SAS set at P ≤ 0.1 using the GLIMMIX procedure. The RS model for MVD and APEH expression were significant (P ≤ 0.0511). However, models for PDHX, GOT2, BCAT1, and GOT1 were not significant (P ≥ 0.1356) and the R2 values ≤ 0.25 for all proteins did not allow for prediction of protein expression means. No linear, quadratic, cross product, or individual BCAA ratio effects were observed for PDHX, GOT2, and BCAT1 (P ≥ 0.1977). A linear model for MVD and APEH protein expression (P ≤ 0.8030) and quadratic model for APEH (P ≤ 0.0552) were significant. MVD increased as Val:Lys ratio increased when Leu:Lys and Ile:Lys were fixed at 148 and 63 or 170 and 70, respectively (P ≤ 0.0926). Low Val:Lys ratio expressed the least hepatic APEH expression when Leu:Lys and Ile:Lys ratios were 148 and 63 or 125 and 70, respectably (P ≤ 0.0153). Hepatic MVD expression decreased as Leu:Lys ratio increased when Val:Lys and Ile:Lys were 75 and 63, respectably (P ≤ 0.0044). GOT1 expression was higher with 170 Leu:Lys ratio compared with 125, when Val:Lys and Ile:Lys ratio were 68 and 70, respectably (P ≤ 0.0460). APEH was greater with a low Ile:Lys ratio when Val:Lys and Leu:Lys were 68 and 125, respectably (P ≤ 0.0786). Varying concentrations of dietary BCAA and their interactions seem to alter hepatic protein expression and may help explain the mechanisms underlying their influence on broiler growth.

265 Interactive Effects of Dietary Isoleucine and Valine Ratios to Lysine in Response to Varying Leucine to Lysine Ratios on Pectoralis Major Muscle Protein Expression in Commercial Broilers

Abstract Optimizing the dietary concentrations and ratios of branched-chain amino acids (BCAA) is necessary to optimize broiler chicken growth performance and carcass meat yield. A central composite design (CCD) study was conducted to understand the impact of dietary BCAA concentrations and ratios on Pectoralis major (PM) muscle protein expression involved in mTOR and related protein synthesis pathways as well as and investigate the mechanisms behind how BCAA ratios affect broiler growth and muscle protein accretion. A total of 2,592 d-old Ross 344 × 708 male broilers were randomly placed in 144 floor pens (n = 18 birds per pen). Before the initiation of the experimental finisher phase, all pens were standardized to contain 15 birds per pen. Each pen received 1 of 15 dietary treatments in the 23 CCD with 6 center points from 20 to 35 d of age, varying in digestible ratios of valine:lysine (Val:Lys; 64 to 87), leucine:lysine (Leu:Lys; 110 to 185), and isoleucine:lysine (Ile:Lys; 52 to 75). On d 35, 1 bird per pen was randomly selected for PM protein extraction and proteomic analysis via data independent acquisition protein sequencing with a timsTOF Pro 2 LC/MS/MS and Spectronaut 15 software. Ribosomal protein S6 kinase (RPS6KA3), eukaryotic elongation factor 2 (EEF2), eukaryotic translation initiation factor 4B (EIF4B), eukaryotic translation initiation factor 4E (EIF4E), CAP-Glycine domain containing linker protein 1 (CLIP1), mitogen-activated protein kinase 3 (MAPK3), Protein kinase domain-containing protein (MAP2K1), Dual-specificity mitogen-activated protein kinase kinase 2 (MAP2K2), paxillin (PXN), and regulator complex protein (LAMTOR3) were identified, quantified, and analyzed as a CCD using the RSREG procedure of SAS ver. 9.4 with significance set at P ≤ 0.10. The surface response models for RPS6KA3, EEF2, EIF4B, EIF4E, MAPK3, MAP2K1, MAP2K2, CLIP1, PXN, and LAMTOR3 were not significant (P ≥ 0.926; R2 values ≤ 0.1). No linear (P ≥ 0.5223), quadratic (P ≥ 0.0.634) or cross product (P ≥ 0.6238) regression effects were observed for any of the proteins analyzed. A minimum stationary point was observed for RPS6KA3, EEF2, MAPK3, and LAMTOR3. However, optimal values for the other proteins could not be obtained due to stationary saddle points. Overall, the results in this study indicate that varying concentrations of dietary BCAA may not impact expression of proteins related to broiler skeletal muscle growth on d 35 following the 15-d treatment period, despite the influence on live performance. This is a limitation of this study and suggests that if the mTOR pathway was involved it was not still differentially up- or down-regulated at this time point. Further investigation and new studies with multiple time points will be required to better understand the mechanisms behind how BCAA impact broiler growth and muscle development.

Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults

BackgroundExisting research provides conflicting evidence regarding the relationship between estimated branched-chain amino acid (BCAA) intake and metabolic, glycemic markers, and anthropometric characteristics. This research seeks to examine the association between estimated dietary BCAA consumption and glycemic, and metabolic markers, as well as anthropometric parameters in adults classified as overweight or obese.MethodsIn this cross-sectional analysis, we gathered data from 465 overweight and obese individuals aged between 18 and 37 years. To evaluate dietary data, we employed the food frequency questionnaire, and the BCAA content in foods was determined via the United States Department of Agriculture website. We utilized ELISA kits to measure fasting blood glucose (FBS) and lipid profile markers, and additionally calculated low-density lipoprotein (LDL) and insulin sensitivity markers. We assessed sociodemographic status, physical activity (PA), and anthropometric attributes through a method recognized as both valid and reliable. For statistical analysis, we conducted analyses of covariance (ANCOVA), making adjustments for variables including sex, PA, age, energy, and body mass index (BMI).ResultsUpon adjusting for confounders, those in the highest tertiles of BCAA intake exhibited an increase in weight, BMI, waist circumference (WC), waist-to-hip ratio (WHR), and fat-free mass (FFM). Conversely, they demonstrated reduced fat mass (FM) (%) and FM (kg) compared to their counterparts in the lowest tertiles (P < 0.05). Additionally, there was a noted association between greater estimated BCAA intake and reduced LDL levels. Nonetheless, our findings did not reveal a significant relationship between dietary BCAA and glycemic indices.ConclusionsFrom our findings, an increased estimated intake of BCAA seems to correlate with diminished serum LDL concentrations. To gain a more comprehensive understanding of this association, it is imperative that further experimental and longitudinal studies be conducted.

Habitual changes in dietary branched-chain amino acids intake are not correlated with exercise-induced glycemia changes in postmenopausal women

Habitual changes in dietary branched-chain amino acids intake are not correlated with exercise-induced glycemia changes in postmenopausal women

Abstract P2104: Branched-chain Amino Acids Are Required For Acquisition Of The Cardiac Myofibroblast Phenotype

Introduction: Branched-chain amino acids (BCAAs) are critical mediators of anabolic signaling and are essential for cell growth. Findings in both animals and humans indicate that intra-cardiac BCAA levels are markedly elevated in the myocardium after infarction. Nevertheless, it remains unclear how BCAAs contribute to processes involved in post-infarction cardiac remodeling, such as fibrosis. The goals of these studies were to evaluate whether BCAAs can regulate collagen production and facilitate myofibroblast transdifferentiation. Methods and Results: To determine how profibrogenic stimuli influence genes critical for BCAA uptake and catabolism, we performed bulk RNA sequencing on fibroblasts isolated from sham and post-infarcted hearts as well as from naïve fibroblasts treated with TGFβ. Compared with fibroblasts from sham hearts, fibroblasts from post-infarcted hearts had higher expression of BCAA transporters ( Slc7a8 , Slc3a2 , Slc38a1 , Slc1a5 ), lower levels of the inhibitory kinase Bckdk , and higher levels of Bckdh complex constituents ( Dbt, Dld ; n=3–6/group;,q&lt;0.05). Similarly, TGFβ elevated Slc3a and Slc38a1 as well as the BCAA catabolic gene, Bcat1 (n=3/group; q&lt;0.05). Culture of cardiac fibroblasts in BCAA-free medium completely prevented TGFβ-induced Col1a1 and periostin upregulation and markedly diminished α-smooth muscle actin abundance (n=3/group; p&lt;0.05). Conclusion: In cardiac fibroblasts, profibrogenic stimuli increase the expression of genes involved in BCAA uptake and catabolism. BCAA availability significantly impacts fibroblast activation by regulating collagen synthesis and myofibroblast transdifferentiation. Ongoing studies will elucidate whether BCAA catabolism contributes to myofibroblast activation and whether lower dietary BCAA levels influence cardiac remodeling after myocardial infarction.

Sex-Specific Correlation Analysis of Branched-Chain Amino Acids in Dietary Intakes and Plasma among Chinese Adults

BackgroundPrevious findings about the influence of dietary intakes of the branched-chain amino acid (BCAA) on their plasma concentrations have been limited and inconsistent, and evidence from the Chinese population was lacking. ObjectivesThis study aimed to investigate the diet-plasma BCAA correlations in Chinese male and female adults. MethodsThis cross-sectional study was based on a nested case-control study within 2 prospective population-based cohorts in Shanghai, China. Diet information was collected by the food frequency questionnaires. Plasma BCAA concentrations were measured by ultraperformance liquid chromatography coupled with tandem mass spectrometry. Spearman correlations and linear regression models were conducted to examine the relationships between dietary BCAA intakes and plasma BCAA. The multivariable model was adjusted for age at the interview, total energy intake, time of blood collection from last meal, dietary patterns, body mass index (in kg/m2), type 2 diabetes, and physical activity. ResultsA total of 322 males (median age of 57.0 y) and 187 females (median age of 60.0 y) were included in this cross-sectional study. The geometric means of dietary intake of leucine, isoleucine, valine, and BCAA were 4937.7, 3029.6, 3268.5, and 11237.4 mg/d in males, and 4125.7, 2567.8, 2754.3, and 9449.4 mg/d in females. The geometric means of plasma concentrations of leucine, isoleucine, valine, and BCAA were 181.9, 65.0, 219.8, and 469.4 μM/L in males and 161.6, 61.1, 206.5, and 431.6 μM/L in females. Only leucine (r = 0.1660, P = 0.0028) and total BCAA (r = 0.1348, P = 0.0155) in males exhibited weak positive correlation coefficients. After adjustment for the covariates, leucine, isoleucine, valine, and total BCAA in dietary intakes and plasma were not correlated in both males and females. ConclusionsIn Chinese male and female adults, dietary intakes are not major determinants of plasma concentrations of BCAA, and plasma concentrations might not be reflected by usual dietary intakes of BCAA.

Association between type 2 diabetes and branched chain amino acids (BCAA); a case-control study.

Several amino acids and their derivatives have been implicated in insulin resistance (IR) and Type 2 Diabetes Mellitus (T2DM). This research sought to establish a relationship between the dietary levels of branched-chain amino acids (BCAA) and the risk of T2DM. This case-control study was carried out on 4200 participants consisting of 589 people with T2DM and 3611 non-diabetic aged 35 to 70 years residents in Sabzevar, Iran. Data on the economic-social, employment status, medical history, lifestyle, and sleep habits were collected via interview. The food frequency questionnaire (FFQ) was used to check the nutritional status. Participants' dietary BCAA consumption was estimated using Nutritionist IV software. A significant negative association between the incidence of T2DM and the dietary levels of BCAAs after adjustment for age and sex (OR = 0.972, CI 95%:0.648-0.996, P = 0.022). The negative association remained significant after additional adjustments for body mass index (BMI) and physical activity (OR = 0.967, CI 95%: 0.943-0.992, P = 0.010). Interestingly, a positive association was found between T2DM and total BCAAs (OR = 1.067, CI 95%: 1.017-1.119, P = 0.008), Isoleucine (OR = 1.248, CI 95%: 1.043-1.494, P = 0.016), Leucine (OR = 1.165, CI 95%: 1.046-1.299, P = 0.006) and Valine (OR = 1.274, CI 95%: 1.088-1.492, P = 0.003) after further adjustment for calorie intake. Our results demonstrate branched-chain amino acids (BCAAs) including isoleucine, leucine, and valine are negatively associated with the incidence of type 2 diabetes (T2DM) after adjusting for age and sex, BMI, and physical activity. However, adjusting for calorie intake reversed the association between T2DM and BCAAs. These findings suggest that the association between BCAAs and T2DM may be influenced by calorie intake. Future longitudinal studies are warranted. The online version contains supplementary material available at 10.1007/s40200-023-01247-9.

Dietary intakes of branched-chain amino acids and plasma lipid profiles among filipino women in Korea: the Filipino Women’s Diet and Health Study (FiLWHEL)

BackgroundThe potential role of dietary branched-chain amino acids (BCAA) in metabolic health, including cardiovascular disease and diabetes, is evolving, and it is yet to be understood if dietary BCAA intakes are associated with plasma lipid profiles or dyslipidaemia. This study tested the association of dietary BCAA intakes with plasma lipid profiles and dyslipidaemia among Filipino women in Korea.MethodsEnergy-adjusted dietary BCAA intakes (isoleucine, leucine, valine, and total BCAA) and fasting blood profiles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were determined in a sample of 423 women enrolled in the Filipino Women’s Diet and Health Study (FiLWHEL). The generalized linear model was applied to estimate least-square (LS) means and 95% confidence intervals (CIs) and compare plasma TG, TC, HDL-C, and LDL-C across tertile distribution of energy-adjusted dietary BCAA intakes at P < 0.05.ResultsMean of energy-adjusted dietary total BCAA intake was 8.3 ± 3.9 g/d. Average plasma lipid profiles were 88.5 ± 47.4 mg/dl for TG, 179.7 ± 34.5 mg/dl for TC, 58.0 ± 13.7 mg/dl for HDL-C, and 104.0 ± 30.5 mg/dl for LDL-C. LS means, and 95% CIs across tertiles of energy-adjusted total BCAA intakes were 89.9 mg/dl, 88.8 mg/dl and 85.8 mg/dl (P-trend = 0.45) for TG, 179.1 mg/dl, 183.6 mg/dl and 176.5 mg/dl (P-trend = 0.48) for TC, 57.5 mg/dl, 59.6 mg/dl and 57.1 mg/dl (P-trend = 0.75) for HDL-C and 103.6 mg/dl, 106.2 mg/dl and 102.3 mg/dl (P-trend = 0.68) for LDL-C. Furthermore, the multivariable-adjusted prevalence ratios and 95% confidence intervals for dyslipidaemia across increasing tertile distribution of energy-adjusted total BCAA intake were; 1.00, 0.67 (0.40, 1.13) and 0.45 (0.16, 1.27; P-trend = 0.03) for the first, second and third tertile, respectively.ConclusionsHigher dietary intakes of BCAA presented a statistically significant inverse trend with the prevalence of dyslipidaemia among Filipino women in this study and testing these associations in longitudinal studies may be necessary to confirm these findings.

Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection.

Branched chain amino acids (BCAA) supplementation may reduce the incidence of liver failure and hepatocellular carcinoma in patients with cirrhosis. We aimed to determine whether long-term dietary intake of BCAA is associated with liver-related mortality in a well-characterized cohort of North American patients with advanced fibrosis or compensated cirrhosis. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. The analysis included 656 patients who completed two Food Frequency Questionnaires. The primary exposure was BCAA intake measured in grams (g) per 1000 kilocalories (kcal) of energy intake (range 3.0-34.8 g/1000 kcal). During a median follow-up of 5.0 years, the incidence of liver-related death or transplantation was not significantly different among the four quartiles of BCAA intake before and after adjustment of confounders (AHR 1.02, 95% CI 0.81-1.27, P-value for trend = 0.89). There remains no association when BCAA was modeled as a ratio of BCAA to total protein intake or as absolute BCAA intake. Finally, BCAA intake was not associated with the risk of hepatocellular carcinoma, encephalopathy or clinical hepatic decompensation. We concluded that dietary BCAA intake was not associated with liver-related outcomes in HCV-infected patients with advanced fibrosis or compensated cirrhosis. The precise effect of BCAA in patients with liver disease warrants further study.

Elevated branched-chain amino acid promotes atherosclerosis progression by enhancing mitochondrial-to-nuclear H2O2-disulfide HMGB1 in macrophages

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE−/− mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H2O2 dependent manner. Scavenging nuclear H2O2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD.

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.

Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr-/-.Leiden mice. Baseline measurements were performed in chow-fed Ldlr-/-.Leiden mice to assess metabolic risk factors, cognition, and brain structure using magnetic resonance imaging. Thereafter, a subgroup was sacrificed, serving as a healthy reference. The remaining mice were fed an HFD and divided into three groups: (i) no exercise, (ii) exercise, or (iii) exercise and dietary BCAA. Mice were followed for 6 months and aforementioned tests were repeated. We found that exercise alone changed cerebral blood flow, attenuated white matter loss, and reduced neuroinflammation compared to non-exercising HFD-fed mice. Contrarily, no favorable effects of exercise on the brain were found in combination with BCAA, and neuroinflammation was increased. However, cognition was slightly improved in exercising mice on BCAA. Moreover, BCAA and exercise increased the percentage of epididymal white adipose tissue and muscle weight, decreased body weight and fasting insulin levels, improved the circadian rhythm, and transiently improved grip strength. In conclusion, BCAA should be supplemented with caution, although beneficial effects on metabolism, behavior, and cognition were observed.

Short-Term Decreasing and Increasing Dietary BCAA Have Similar, but Not Identical Effects on Lipid and Glucose Metabolism in Lean Mice.

Branched-chain amino acids (BCAA) showed multiple functions in glycolipid metabolism and protein synthesis. However, the impacts on the metabolic health of low or high dietary BCAA remain controversial due to the various experimental conditions. Gradient levels of BCAA were supplemented in lean mice for four weeks: 0BCAA (without BCAA), 1/2BCAA (half BCAA), 1BCAA (regular BCAA), and 2BCAA (double BCAA). The results showed that the diet without BCAA caused energy metabolic disorders, immune defects, weight loss, hyperinsulinemia, and hyperleptinemia. 1/2BCAA and 2BCAA diets reduced body fat percentage, but 1/2 BCAA also decreased muscle mass. 1/2BCAA and 2BCAA groups improved lipid and glucose metabolism by affecting metabolic genes. Meanwhile, significant differences between low and high dietary BCAA were observed. The results of this study provide evidence and reference for the controversy about dietary BCAA levels, which indicates that the main difference between low and high BCAA dietary levels may present in the longer term.

Dietary consumption of branched-chain amino acids among Chinese middle-aged and elderly population aged 50 and over in 2015

To investigate the dietary consumption of branched-chain amino acids(BCAAs)intake status of middle-aged and elderly people 50 years and older in China, and to analyze the distribution differences between different ages, genders and regions. The research sample was derived from the 2015 Chinese adult chronic disease and nutrition monitoring data. The survey adopts the stratified multi-stage cluster random sampling method, and selects 298 monitoring points from 31 provinces(autonomous regions and municipalities), a total of 44 218 people aged 50 years and over were sampled. Condiment weighing method, 24-hour dietary review method, and weighing method were used to obtain individual dietary data, and the dietary BCAAs intake of middle-aged and elderly people was calculated based on the Chinese Food Composition Table. In 2015, the dietary BCAAs of middle-aged and elderly people in China accounted for 45.1% of leucine, 29.8% of valine and 25.1% of isoleucine. The top six dietary sources were cereals, red meat, vegetables, fish and seafood, beans and eggs. There were differences in the intake of three branched-chain amino acids(F=1926.67, P&lt;0.01), the intake of leucine was greater than that of valine, and the intake of valine was greater than isoleucine. There were statistically significant differences in dietary BCAAs intake between different age groups, genders, urban and rural areas and regions(P&lt;0.01), among which men were greater than women(t=12.89, P&lt;0.01), and the south was greater than the north(t=-6.36, P&lt;0.01), the eastern part was larger than the central part, and the central part was larger than the western part(F=82.42, P&lt;0.01). The intake of BCAAs decreased with the increase of age groups(F=22.69, P&lt;0.01), and there was no significant difference in age groups over 70 years old. The dietary intake of BCAAs was higher in the eastern coastal areas and Inner Mongolia, Xinjiang and Tibet. There were gender, age and geographical differences in dietary BCAAs intake among middle-aged and elderly people in China, and the contribution of various foods to dietary BCAAs was also different.