Association of Dietary Branched-Chain Amino Acids With Obesity: The Filipino Women's Diet and Health Study (FiLWHEL)

Abstract Objectives Migration plays a significant role in dietary choices and health of populations. Studies on dietary intakes of branched-chain amino acids (BCAA) and health status of migrant populations are scarce. This study examined the association between dietary BCAA intake and risk of obesity among migrant Filipino women in Korea. Methods This study included 428 women (20–57years) enrolled in the FiLWHEL study. Demographic information and anthropometric measurements (weight and height) were obtained using a standard protocol. Dietary BCAA (isoleucine, leucine, and valine) intakes were derived from a one-day 24-hour dietary recall. Body mass index (BMI) was calculated from weight and height. Obesity was defined as BMI ≥ 25 kg/m2. Energy-adjusted BCAA intakes were categorized in quartile distribution with the lowest quartile as a reference and multivariable-adjusted odds ratio (OR) with 95% confidence interval (CI) of obesity risk were estimated using logistic regression at a statistical significance of P < 0.05. Results Mean age and BMI were 35.0 ± 8.1 years and 23.6 ± 3.9 kg/m2 respectively. 30.8% had BMI ≥ 25 kg/m2. Also, median and interquartile range of BCAA intakes (mg/day) were isoleucine: 1920.9 (1231.9–2719.1), leucine: 3318.9 (2134.2–4774.1), valine: 2257.3 (1442.6–3283.1) and total BCAA: 7519.0 (4762.0–10,726.9). Multivariable-adjusted OR and 95% CI for obesity risk given dietary BCAA intakes for each subsequent quartile compared to the bottom quartile were; isoleucine: 0.48 (0.27–0.89), 0.67 (0.37–1.02), and 0.49 (0.27–0.89) P for trend = 0.09; leucine: 0.69 (0.37–1.28), 0.80 (0.44–1.46), and 0.62 (0.34–1.13) P for trend = 0.23; valine: 0.51 (0.27–0.95), 0.77 (0.43–1.37), and 0.52 (0.28–0.95) P for trend = 0.15 and total BCAA: 0.58 (0.31–1.09), 0.82 (0.45–1.48), and 0.56 (0.31–1.03) P for trend = 0.23. Conclusions Dietary BCAA intake appears inversely related to the odds of obesity in this sample of Filipino migrants in Korea. Cohort studies among migrant population might significantly benefit the validation of these observations. Funding Sources This work was supported by the Hanmi Pharmaceutical Co., Ltd, (No. 201300000001270), Chong Kun Dang Pharm. Seoul, Korea (No. 201600000000225) and the Brain Pool Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (No. 2020H1D3A1A04081265).

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Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women

Circulation ◽

10.1161/circ.137.suppl_1.048 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Deirdre K Tobias ◽

Patrick R Lawler ◽

Paulo H Harada ◽

Olga V Demler ◽

Paul M Ridker ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Amino Acids ◽

Prospective Cohort ◽

Branched Chain Amino Acids ◽

Health Study ◽

Blood Collection ◽

Cvd Risk ◽

Isoleucine Leucine ◽

Branched Chain

Introduction: Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established. Hypothesis: We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D. Methods: Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization). Results: 1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p<0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD. Conclusions: Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.

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A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes

Nutrients ◽

10.3390/nu13010095 ◽

2020 ◽

Vol 13 (1) ◽

pp. 95

Author(s):

Imran Ramzan ◽

Moira Taylor ◽

Beth Phillips ◽

Daniel Wilkinson ◽

Kenneth Smith ◽

...

Keyword(s):

Amino Acids ◽

Pilot Study ◽

Dietary Intervention ◽

Control Diet ◽

Branched Chain Amino Acids ◽

Model Assessment ◽

Dietary Intakes ◽

Restricted Diet ◽

Obesity And Diabetes ◽

Branched Chain

Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.

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Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis

Acta Diabetologica ◽

10.1007/s00592-018-1243-7 ◽

2018 ◽

Vol 56 (2) ◽

pp. 187-195 ◽

Cited By ~ 9

Author(s):

Akinkunmi Paul Okekunle ◽

Meng Zhang ◽

Zhen Wang ◽

Justina Ucheojor Onwuka ◽

Xiaoyan Wu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Meta Analysis ◽

Branched Chain Amino Acids ◽

Obesity Risk ◽

Branched Chain ◽

Diabetes And Obesity

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Bootstrapped neural network models for analyzing the responses of broiler chicks to dietary protein and branched chain amino acids

Canadian Journal of Animal Science ◽

10.4141/cjas2013-078 ◽

2014 ◽

Vol 94 (1) ◽

pp. 79-85 ◽

Cited By ~ 5

Author(s):

A. Faridi ◽

A. Golian ◽

A. Heravi Mousavi ◽

J. France

Keyword(s):

Neural Network ◽

Amino Acids ◽

Dietary Protein ◽

Average Daily Gain ◽

Network Models ◽

Branched Chain Amino Acids ◽

Broiler Chicks ◽

Neural Network Models ◽

Isoleucine Leucine ◽

Branched Chain

Faridi, A., Golian, A., Heravi Mousavi, A. and France, J. 2014. Bootstrapped neural network models for analyzing the responses of broiler chicks to dietary protein and branched chain amino acids. Can. J. Anim. Sci. 94: 79–85. Reliable prediction of avian responses to dietary nutrients is essential for planning, management, and optimization activities in poultry nutrition. In this study, two bootstrapped neural network (BNN) models, each containing 100 separated neural networks (SNN), were developed for predicting average daily gain (ADG) and feed efficiency (FE) of broiler chicks in response to intake of protein and branched chain amino acids (BCAA) in the starter period. Using a re-sampling method, 100 different batches of data were generated for both the ADG and FE sets. Starting with 270 data lines extracted from eight studies in the literature, SNN models were trained, tested, and validated with 136, 67, and 67 data lines, respectively. All 200 SNN models developed, along with their respective BNN ones, were subjected to optimization (to find the optimum dietary protein and BCAA levels that maximize ADG and FE). Statistical analysis indicated that based on R 2, the BNN models were more accurate in 76 and 56 cases (out of 100) compared with the SNN models developed for ADG and FE, respectively. Optimization of the BNN models showed protein, isoleucine, leucine, and valine requirements for maximum ADG were 231.80, 9.05, 14.03 and 10.90 g kg−1 of diet, respectively. Also, maximum FE was obtained when the diet contained 232.30, 9.07, 14.50, and 11.04 g kg−1 of protein, isoleucine, leucine, and valine, respectively. The results of this study suggest that in meta-analytic modelling, bootstrap re-sampling algorithms should be used to better analyze available data and thereby take full advantage of them. This issue is of importance in the animal sciences as producing reliable data is both expensive and time-consuming.

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Association of dietary intake of branched-chain amino acids with long-term risks of cardiovascular disease, cancer and all-cause mortality

Public Health Nutrition ◽

10.1017/s1368980021004948 ◽

2021 ◽

pp. 1-60

Author(s):

Binbin Xu ◽

Meng Wang ◽

Liyuan Pu ◽

Chang Shu ◽

Lian Li ◽

...

Keyword(s):

Cardiovascular Disease ◽

Amino Acids ◽

Dietary Intake ◽

The United States ◽

Branched Chain Amino Acids ◽

Dietary Intakes ◽

All Cause Mortality ◽

Nationally Representative ◽

Branched Chain

Abstract Objectives: Studies on associations between dietary intake of branched-chain amino acids (BCAAs) and long-term risks of cardiovascular disease (CVD), cancer, and all-cause mortality have yielded inconclusive results. This study aimed to investigate the associations between dietary BCAA intake and long-term risks of CVD, cancer, and all-cause mortality in nationwide survey participants aged ≥18. Design: This was a prospective cohort study of a nationally representative sample of 14,397 adults aged ≥18 who participated in the United States National Health and Nutrition Examination Survey III (NHANES III). Dietary intakes of BCAAs (leucine, isoleucine, and valine) were determined from the total nutrient intake document. The main outcomes were CVD, cancer, and all-cause mortality. Results: During 289,406 person-years of follow-up, we identified 4,219 deaths, including 1,133 from CVD and 926 from cancer. After multivariate adjustment, the hazard ratios (95% confidence intervals) of all-cause mortality in the highest dietary BCAA and isoleucine intake quintile (reference: lowest quintiles) were 0.68 (0.48–0.97) and 0.68 (0.48–0.97), respectively. Each one-standard-deviation increase in total dietary BCAA or isoleucine intake was associated with an 18% or 21% decrease in the risk of all-cause mortality, respectively. The serum triglyceride (TG) concentration was found to modify the association between the dietary BCAA intake and all-cause mortality (P for interaction = 0.008). Conclusions: In a nationally representative cohort, higher dietary intakes of BCAAs and isoleucine were independently associated with a lower risk of all-cause mortality, and these associations were stronger in participants with higher serum TG concentrations.

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Genetic predisposition to impaired metabolism of the branched chain amino acids, dietary intakes, and risk of type 2 diabetes

Genes & Nutrition ◽

10.1186/s12263-021-00695-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weiqi Wang ◽

Zengjiao Liu ◽

Lin Liu ◽

Tianshu Han ◽

Xue Yang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Genetic Predisposition ◽

Metabolic Pathway ◽

Regression Models ◽

Branched Chain Amino Acids ◽

Diabetes Incidence ◽

Dietary Intakes ◽

Branched Chain

Abstract Background and objectives Circulating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters. Methods We estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c. Results Dietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 μmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals. Conclusions Our study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility.

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The Relationship between S. aureus and Branched-Chain Amino Acids Content in Composite Cow Milk

Animals ◽

10.3390/ani9110981 ◽

2019 ◽

Vol 9 (11) ◽

pp. 981 ◽

Cited By ~ 1

Author(s):

L. Grispoldi ◽

M. Karama ◽

F. Ianni ◽

A. La Mantia ◽

L. Pucciarini ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid Content ◽

Branched Chain Amino Acids ◽

Cow Milk ◽

Total Amino Acid ◽

Phase Method ◽

Microbiological Analysis ◽

Isoleucine Leucine ◽

Milk Samples ◽

Branched Chain

The early diagnosis of mastitis is an essential factor for the prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. The total amino acid content increases significantly in mastitic milk compared to normal milk. S. aureus requires branched-chain amino acids (BCAAs—isoleucine, leucine, and valine) for protein synthesis, branched-chain fatty acids synthesis, and environmental adaptation by responding to their availability via transcriptional regulators. The increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. The aim of this work is to demonstrate, by a direct ion-pairing reversed-phase method, based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine, and S. aureus load. The correlation coefficient, r, was found to be 0.102 for SCC (p = 0.096), 0.622 for isoleucine (p < 0.0001), 0.586 for leucine (p < 0.0001), 0.013 for valine (p = 0.381), and 0.07 for tyrosine (p = 0.034), standing for a positive correlation between S. aureus and isoleucine and leucine concentration. The link between the content of BCAAs, isoleucine and leucine, and udder infection by S. aureus demonstrated with our study has an important clinical value for the rapid diagnosis of S. aureus mastitis in cows.

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Free carnitine and branched chain amino acids are not good biomarkers in Huntington’s disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190152 ◽

2020 ◽

Vol 78 (2) ◽

pp. 81-87

Author(s):

Raphael Machado CASTILHOS ◽

Marina Coutinho AUGUSTIN ◽

José Augusto dos SANTOS ◽

José Luiz PEDROSO ◽

Orlando BARSOTTINI ◽

...

Keyword(s):

Amino Acids ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Age Of Onset ◽

Branched Chain Amino Acids ◽

Free Carnitine ◽

Cag Repeat ◽

Isoleucine Leucine ◽

Branched Chain

ABSTRACT Background: Huntington’s disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. Objective: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. Methods: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. Results: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. Conclusions: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

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Regulation of CodY Activity through Modulation of Intracellular Branched-Chain Amino Acid Pools

Journal of Bacteriology ◽

10.1128/jb.00937-10 ◽

2010 ◽

Vol 192 (24) ◽

pp. 6357-6368 ◽

Cited By ~ 43

Author(s):

Shaun R. Brinsmade ◽

Roelco J. Kleijn ◽

Uwe Sauer ◽

Abraham L. Sonenshein

Keyword(s):

Amino Acids ◽

Bacterial Species ◽

Regulatory Protein ◽

Fold Increase ◽

Acid Synthesis ◽

Branched Chain Amino Acids ◽

Nucleoside Triphosphate ◽

Isoleucine Leucine ◽

Branched Chain

ABSTRACT In several Gram-positive bacterial species, the global transcriptional regulatory protein CodY adjusts the expression of many metabolic genes, apparently in response to changes in the pools of specific metabolites, i.e., the branched-chain amino acids (BCAAs) isoleucine, leucine, and valine (ILV) and the nucleoside triphosphate GTP. CodY not only responds to these metabolites as measured in vitro but also regulates the genes that direct their synthesis. We have constructed a set of strains lacking binding sites for the CodY protein in cis at loci coding for the ILV biosynthetic machinery, effectively overexpressing these genes in an attempt to modulate the ILV input signal to CodY. Metabolite analyses of strains derepressed for genes needed for ILV synthesis revealed more than a 6-fold increase in the valine pool and a 2-fold increase in the isoleucine and leucine pools. Accumulation of the branched-chain amino acids was accompanied by a 24-fold induction of the bkd operon (required for branched-chain fatty acid synthesis) and 6-fold hyperrepression of the CodY-regulated yhdG and yufN genes, demonstrating that CodY perceives intracellular fluctuations in at least one if its input signals. We conclude that changes in the rate of endogenous ILV synthesis serve as an important signal for CodY-mediated gene regulation.

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Determination of branched-chain amino acids and tyrosine in serum of patients with various hepatic diseases, and its clinical usefulness.

Clinical Chemistry ◽

10.1093/clinchem/35.7.1399 ◽

1989 ◽

Vol 35 (7) ◽

pp. 1399-1403 ◽

Cited By ~ 57

Author(s):

Y Azuma ◽

M Maekawa ◽

Y Kuwabara ◽

T Nakajima ◽

K Taniguchi ◽

...

Keyword(s):

Amino Acids ◽

Clinical Laboratory ◽

Branched Chain Amino Acids ◽

Isoleucine Leucine ◽

Hepatic Diseases ◽

Enzymatic Determination ◽

Branched Chain ◽

Routine Clinical Laboratory ◽

Parenchymal Damage

Abstract We developed an automated enzymatic method for determination of the branched-chain amino acids (BCAAs; valine, isoleucine, leucine) and tyrosine in serum, and applied it to the clinical evaluation of patients with various hepatic diseases. Analytically, the test results were acceptably precise and reproducible, and correlated well with results obtained with an amino acid analyzer. Clinically, we found that a decrease in BCAAs, an increase in tyrosine, and the BCAAs/tyrosine ratio in serum paralleled the severity of hepatic parenchymal damage. We conclude that this enzymatic determination of BCAAs and tyrosine is simple and convenient enough for routine clinical laboratory use, and that the ratio of BCAAs/tyrosine obtained may be a good indicator of the severity of hepatic disorders.

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