Total Branched-chain Amino Acids Research Articles

Novel insights of phenylalanine in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and cardiovascular complications

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cardiovascular risk, necessitating an exploration of potential metabolic contributors, such as amino acids. While amino acids are implicated in metabolic disorders, their specific relationship with MASLD and subsequent cardiovascular complications is not well-defined. We aimed to delineate the association between circulating amino acids and MASLD, identifying amino acids that could potentially link MASLD to cardiovascular issues. Methods Utilizing UK Biobank data, we tested the association of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Afterwards, we performed Mendelian Randomization (MR) using genome-wide association study (GWAS) data from 8,434 MASLD cases and 770,180 controls, and GWAS of amino acids including 115,052 participants from UK Biobank. Multiple MR methods, including MR-Egger, Cochran's Q-test, and MR-PRESSO, were applied to assess pleiotropy and heterogeneity. Survival analysis in MASLD patients assessed the link between significant amino acid and incident severe cardiovascular outcomes, including stroke, heart failure, myocardial infarction, and mortality, using three different covariate combinations: Model 1 included age, sex, and fasting time; Model 2 included in addition smoking, alcohol use, education, physical activity, and Model 3 included body mass index (BMI) in addition to model 2. Results Nine out of the ten amino acids were statistically significantly associated with MASLD across all three models (p<6.25×10^-3). Among them valine, leucine, isoleucine, total branched-chain amino acids, tyrosine, alanine, and phenylalanine were positively associated with MASLD, while glutamine and glycine were negatively associated with MASLD. The genetic predisposition of MASLD was significantly associated with increased phenylalanine (beta=0.05, p=4.0×10^-4) and tyrosine (beta=0.15, p=2.0×10^-3), suggesting that alterations in these amino acids may result from the progression of MASLD. We also detected heterogeneity (Cochran’s Q-test: p=8.4×10^-9) and pleiotropy (MR-Egger: p=0.02) for tyrosine, but not for phenylalanine. Furthermore, phenylalanine levels in MASLD patients were significantly (p<6.25×10^-3) associated with the incidence of heart failure, stroke, and mortality, but not with myocardial infarction across all three models. We did not identify a significant association between baseline tyrosine levels and any cardiovascular complications or mortality across the three models (Figure 1). Conclusion Our findings indicate a strong association between certain amino acids and MASLD, with phenylalanine, in particular, emerging as a potential mediator of cardiovascular risk in MASLD patients. The absence of heterogeneity and pleiotropy for phenylalanine strengthens its candidacy as a biomarker for future cardiovascular complications in MASLD.

Branched-chain amino acids and risk of lung cancer: insights from mendelian randomization and NHANES III.

Recent studies have observed the relationships of circulatory and dietary intake of branched-chain amino acids (BCAAs) with long-term risk of certain cancers. However, the exact causality of BCAA with lung cancer (LUCA) and its pathological subtypes remains obscure. The aim of this study is to investigate the association between BCAA metabolism and risk of LUCA. Here we conducted Mendelian randomization (MR) and observational epidemiological analyses to investigate the association between BCAA and risk of LUCA. With single nucleotide polymorphism (SNP)-phenotype association data extracted from genome-wide association studies (GWAS), we performed univariate and multivariate MR analyses to infer the causal effect of circulatory BCAA concentrations on LUCA. We further investigated the effects of several potential mediators and quantified the mediation effects. Population-level analyses were performed in the National Health and Nutrition Examination Survey (NHANES) III. Our results demonstrated that genetically predicted circulatory valine concentrations causally increased the risk of overall LUCA [odds ratio (OR) =1.324, 95% confidence interval (CI): 1.058-1.658, P=0.01]. For pathological subgroups, elevated levels of leucine, isoleucine, valine, and total BCAA were founded to be significantly associated with a higher risk of squamous cell lung cancer (LUSC); however, they did not significantly affect lung adenocarcinoma (LUAD). Moreover, body mass index (BMI) mediated approximately 3.91% (95% CI: 1.22-7.18%) of the total effect of leucine on LUSC. In the NHANES III population, dietary total BCAA intake was significantly associated with BMI ≥30 kg/m2, while no non-linear relationships were observed. This study provides genetic evidence for the histology-specific causality of BCAA on LUCA and implies the mediation role of BMI in this relationship. Further studies are needed to confirm these findings and elucidate the underlying mechanisms.

An interplay between plasma glycine and total branched-chain amino acids contributes to the development of hypertension and ischaemic heart disease

An interplay between plasma glycine and total branched-chain amino acids contributes to the development of hypertension and ischaemic heart disease

Leucine requirement determined in healthy young adult males using the indicator amino acid oxidation method

BackgroundPrevious studies proposed varying leucine requirements for adults ranging from 25 to 40 mg⋅kg−1⋅d−1, but often these studies did not test intakes exceeding 40 mg⋅kg−1⋅d−1. Data using the indicator amino acid oxidation (IAAO) method suggest a higher requirement of 55 mg⋅kg−1⋅d−1 on the basis of the total branched-chain amino acids requirement, but not leucine independently. ObjectivesThe IAAO method was used to determine the leucine requirement in healthy young adult males. MethodsTen healthy adult males (26.9 ± 1.87 y, mean ± SEM) were studied at 7 leucine intakes; each studied over a 3-d period. Following 2-d of preadaptation to adequate protein intake (1.0 g⋅kg−1⋅d−1), subjects received experimental diets containing the randomly assigned test leucine intake (10, 20, 30, 40, 50, 65, and 75 mg⋅kg−1⋅d−1) for 8 h. The rate of the release of 13CO2 from the oxidation of L-[1-13C]phenylalanine (F13CO2) was measured on the third day, and the leucine requirement was determined using mixed-effect change-point regression and the F13CO2 data in R. The 95% confidence interval was calculated using parametric bootstrap. The effect of leucine intake on the concentration of plasma amino acids, insulin, and glucose were assessed using repeated measures analysis of variance and linear mixed effects. ResultsThe mean leucine requirement was 33.6 mg⋅kg−1⋅d−1 with a lower and upper 95% confidence of 26.16, 41.04 mg⋅kg−1⋅d−1. Higher leucine intakes were associated with increased plasma leucine, and decreased valine, isoleucine, and serine concentrations. ConclusionsThe leucine requirement of young adult males is ∼34 mg⋅kg−1⋅d−1, which aligns with previously published tracer balance experiments.This trial was registered at http://clinicaltrials.gov (https://clinicaltrials.gov/study/NCT05394155?term=leucine%20young%20adult&rank=1) as NCT05394155.

Serum Branched-Chain Amino Acids and Long-Term Complications of Liver Cirrhosis: Evidence from a Population-Based Prospective Study.

The role of serum branched-chain amino acids (BCAAs) in long-term liver cirrhosis complication events remains unclear. We aimed to evaluate the associations between serum BCAAs and the risk of liver-related events. We included a total of 64,005 participants without liver cirrhosis complication events at baseline from the UK Biobank. Cox proportional hazards regression models were utilized to estimate multivariable hazard ratios (HRs) and 95% CIs for the incidence of liver cirrhosis complication events, adjusting for potential confounders, including sociodemographic and lifestyle factors. Relationships between serum BCAAs and liver cirrhosis complications were examined using nonparametrically restricted cubic spline regression. During a median follow-up of 12.7 years, 583 participants developed liver cirrhosis complication events. The multivariable Cox regression model suggested that total BCAAs (HR = 0.88, 95% CI 0.82-0.95), serum leucine (HR = 0.88, 95% CI 0.81-0.95), serum isoleucine (HR = 0.88, 95% CI 0.82-0.96), and serum valine (HR = 0.87, 95% CI 0.82-0.96) were all independent protective factors for liver cirrhosis complications after adjustment for sociodemographic and lifestyle factors. Cox models with restricted cubic splines showed U-shaped associations between serum valine and liver cirrhosis complication incidence. Serum total BCAA and isoleucine concentrations might reduce the risk of liver cirrhosis complications by raising the risk of (type 2 diabetes mellitus) T2DM. Lower serum BCAA levels exacerbate the long-term risk of liver cirrhosis complications. Future studies should confirm these findings and identify the biological pathways of these associations.

Sex differences in the association between plasma branched-chain amino acids and risk of ischemic stroke: A nested case-control study from China

ObjectivesThe aim of this study was to investigate the prospective associations between plasma branched-chain amino acids (BCAAs) and the risk of ischemic stroke in men and women. MethodsWe conducted a nested case-control study within a community-based cohort in China. The cohort consisted of 15,926 participants in 2013-2018. A total of 321 ischemic stroke cases were identified during the follow up and individually matched with 321 controls by date of birth (±1 year) and sex. Females accounted for 55.8% (n = 358, 179 cases vs 179 controls) of the study population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between plasma BCAAs and ischemic stroke risk by conditional logistic regression. ResultsElevated plasma isoleucine was associated with a higher risk of ischemic stroke in women. The OR for the highest compared to the lowest quartile was 2.22 (95% CI: 1.11-4.44, P trend = 0.005) after adjustment for body mass index, education attainment, smoking, hypertension, renal function, menopause and physical activity. A similar association was found for total BCAAs (adjusted OR = 2.03, 95% CI: 1.05-3.95, P trend = 0.04). In contrast, no significant association of plasma BCAAs with ischemic stroke risk was observed in men. ConclusionsPlasma isoleucine and total BCAAs were significantly associated with ischemic stroke risk in women, but not in men, highlighting sex differences in BCAAs metabolism and stroke pathogenesis.

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study.

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096-1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07-11.99%), the fatty acid group (4.78-12.82%), and the cholesterol group (3.64-11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.

Dietary and circulating branched chain amino acids are unfavorably associated with body fat measures among Chinese adults

Animal studies showed a detrimental effect of dietary branched chain amino acids (BCAAs) on metabolic health, while epidemiological evidence on dietary BCAAs and obesity is limited and inconclusive. We hypothesized that high dietary and circulating BCAAs are unfavorably associated with obesity in community-dwelling adults. We evaluated the 1-year longitudinal associations of dietary BCAA intake and circulating BCAAs with body fat measures. Body weight, height, and circumferences of the waist (WC) and hip (HC) were measured at baseline and again after 1-year. Body composition and liver fat [indicated by controlled attenuation parameter (CAP)] were also assessed after 1-year. Serum BCAA concentrations at baseline were quantified by liquid chromatography mass spectrometry. Diet was collected using 4 quarterly 3-day recalls during the 1-year. The correlation coefficients between dietary and serum BCAAs were 0.12 (P = .035) for total dietary BCAAs, and ranged from -0.02 (soy foods, P = .749) to 0.18 (poultry, P = .001). Total dietary BCAA intake was associated with increase in body weight (β = 0.044, P = .022) and body mass index (BMI, β = 0.047, P = .043). BCAAs from animal foods were associated with increase in HC, while BCAAs from soy foods were associated with weight gain and higher CAP (all P < .05). Serum BCAAs were associated with higher WC, HC, BMI, body fat mass, visceral fat level, and CAP (all P < .05). These results support that dietary and circulating BCAAs are positively associated with the risk of obesity. More cohort studies with validated dietary assessment tools and long-term follow-up among diverse populations are needed to confirm our findings.

Associations of Dietary and Circulating Total Branched-Chain Amino Acids With Obesity Among Filipino Women

Associations of Dietary and Circulating Total Branched-Chain Amino Acids With Obesity Among Filipino Women

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.

17 Effect of branched-chain amino acids on lactating sow and piglet performance

Abstract Sows (n = 360 PIC 1050 and Genesus) were used to investigate the effect of various branched-chain amino acid (BCAA) levels on sow lactation and litter growth performance. Upon entering the farrowing room, sows were blocked by parity group (P0, P2, P3+) and randomly assigned to one of six dietary treatments containing various levels of BCAA. Experimental diets were formulated to various standardized ileal digestible (SID) leucine, isoleucine, and valine levels by replacing cornstarch with L-leucine, L-isoleucine, and L-valine. Levels of the BCAA were expressed as ratios to SID lysine and were formulated at 114 or 180 for Leu, 56 or 64 for Ile, and 64 or 120 for Val. Diets were formulated to be isocaloric (3.23 Mcal ME/kg) and met or exceeded all other NRC (2012) essential amino acid and vitamin and mineral recommendations. Sow body weight (BW), backfat, and body condition score were recorded at the time of entry into the farrowing room and at the time of weaning. Piglet litter weights were recorded after cross-fostering and at weaning to determine litter growth rate. Data were analyzed using generalized linear mixed models with fixed effects of dietary treatment and parity group and a random effect of lactation group. The models were fit using R version 4.3.1 (R Core Team, 2023). The sow and her litter were the experimental unit, and results were considered significant if P ≤ 0.05 and a tendency if 0.05 &amp;lt; P ≤ 0.10. Sows nursed piglets for 21.3 d (P = 0.998). The mean parity by treatment ranged from 3.8 to 3.9 (P = 0.999). After farrowing, the mean estimated sow BW was 219 kg, with a range between treatments of 216 to 221 kg (P = 0.651). On average, sows gained 2.82% of their BW (P = 0.696) with an average daily feed intake (ADFI) of 8.75 kg/d (P = 0.932). However, as expected, sow Leu, Ile, Val, and total BCAA intakes were different across treatments (P ≤ 0.001). Sows entered the farrowing house with an average of 11.50 mm of backfat (P = 0.919) and lost 6.04% backfat through lactation (P = 0.667). Sows started the trial with an average of 14.1 piglets/sow (P = 0.967) and weaned 12.6 piglets per sow (P = 0.981) with a piglet average daily gain of 0.22 kg/d (P = 0.193) and a daily litter growth rate of 2.89 kg/d (P = 0.291). In conclusion, there was no evidence of an effect of the various leucine, isoleucine, and valine levels evaluated in this study on lactating sow and piglet performance.

Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease.

Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. P-gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D. The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (P-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively). The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802). Referent subjects included participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) study (n=5241). GlycA, BCAA, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes mellitus and statin therapy. In age-and sex-adjusted comparison to referent subjects, increased GlycA was noted in all patient categories, increased BCAA in NFA, MACS, CS, PA and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of subjects with diabetes and cardiovascular disease. Patients with functioning and non-functioning adrenal masses demonstrated increased GlycA and BCAA, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

Metabolomics and gut metagenomics profile of the healthy adults on consumption of whey protein supplemented with enzymes-probiotics blend

In this randomized, crossover, pilot clinical study, we aimed to evaluate the effect of supplementation of enzymes-probiotics blend with whey protein on the amino acid absorption and gut microbiota. Healthy subjects were supplemented with the whey protein and test i.e. Pepzyme Pro (enzymes-probiotics blend) or placebo i.e. maltodextrin for 15 days with the washout period of 30 days. Blood samples were analyzed for plasma free amino acids, insulin, and CRP. Additionally, urine nitrogen, fecal nitrogen, and gut microbiota were evaluated. On day 15, the test arm showed upward trend in rate of amino acid absorption than placebo arm within 30 min of post ingestion of protein. Moreover, rate of absorption of few essential and branched chain amino acids were significantly higher (methionine (p = 0.049), leucine (p = 0.014), isoleucine (p = 0.053)) in the test arm on day 15. Total branched chain amino acids absorption were found to be significantly higher (p ≤ 0.05) in the test arm than the placebo arm within 30 min of post ingestion on day 15. Uptrend in total amino acid absorption and Cmax, and downtrend in Tmax was observed on day 15 in the test arm. The CRP, fecal nitrogen, and urine nitrogen remained unaltered after supplementation. Microbiota profiling showed significant change in abundance of species of genus Bacteroides and phylum Bacteroidetes. Overall, metagenomics and metabolomics based assessments demonstrated that the consumption of Pepzyme Pro with whey protein could potentially improve protein digestion, amino acid absorption, and modulate gut microbiota.Clinical trial registration The clinical trial registry of India CTRI/2021/09/036169 [Registered on: 02/09/2021]

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.

The Association Between Branched-Chain Amino Acid Concentrations and the Risk of Autism Spectrum Disorder in Preschool-Aged Children

Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with autism spectrum disorder (ASD), but the results have been inconsistent. The purpose of this study was to explore the association between BCAA concentrations and the risk of ASD. A total of 313 participants were recruited from two tertiary referral hospitals from May 2018 to July 2021. Concentrations of BCAAs in dried blood spots were analyzed using liquid chromatography-tandem mass spectrometry-based analysis. Multivariate analyses and restricted cubic spline models were used to identify the association between BCAAs and the risk of ASD, and a nomogram was developed by using multivariate logistic regression and the risk was determined by receiver operating characteristic curve analysis and calibration curve analysis. Concentrations of total BCAA, valine, and leucine/isoleucine were higher in the ASD group, and all of them were positively and non-linearly associated with the risk of ASD even after adjusting for potential confounding factors such as age, gender, body mass index, and concentrations of BCAAs (P < 0.05). The nomogram integrating total BCAA and valine showed a good discriminant AUC value of 0.756 (95% CI 0.676–0.835). The model could yield net benefits across a reasonable range of risk thresholds. In the stratified analysis, the diagnostic ability of the model was more pronounced in children older than 3 years. We provide evidence that increased levels of BCAAs are associated with the risk of ASD, and the nomogram model of BCAAs presented here can serve as a marker for the early diagnosis of ASD.

Intake of dietary branched-chain amino acids reduces odds of metabolic syndrome: a cross-sectional study on the PERSIAN Kavar cohort study.

Metabolic syndrome (MetS) is identified by the manifestation of a minimum of three out of five metabolic abnormalities, including insulin resistance, hypertension, hypertriglyceridemia, abdominal obesity, and low levels of high-density lipoprotein cholesterol. The present study aimed to assess the association between dietary branched-chain amino acids (BCAA) intakes and MetS, due to available conflicting evidence. A total of 4,860 individuals who had participated in the baseline phase of the PERSIAN (Prospective Epidemiological Research Studies in IrAN) Kavar cohort study were included in our study. The daily intake of valine, leucine, and isoleucine were evaluated using a semi-quantitative food frequency questionnaire. The association between dietary BCAA intake with MetS and its components was evaluated using logistic regression analysis. The mean intake of BCAA among the included subjects was 7.65 (standard deviation [SD]: 2.92), and the prevalence of MetS was found to be 49.2%. Multivariable logistic regression analysis revealed an inverse association between 1-S.D. increment in dietary valine (odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.78-0.94), leucine (OR = 0.85, 95% CI: 0.77-0.93), isoleucine (OR = 0.84, 95% CI: 0.76-0.93), and total BCAA (OR = 0.85, 95% CI: 0.77-0.93) intake and the odds of MetS. There were also a significant association between BCAA intakes and hyperglycemia and hypertriglyceridemia. We observed a significant inverse association between dietary BCAA intake and MetS, hyperglycemia, and hypertriglyceridemia, regardless of confounding factors.

Maternal glycemic status during pregnancy and mid-childhood plasma amino acid profiles: findings from a multi-ethnic Asian birth cohort

BackgroundIncreasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers.MethodsData were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother–child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26–28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores.ResultsApproximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood.ConclusionsIncreasing maternal fasting and post-OGTT glucose concentrations at 26–28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

FRI071 Changes In Branched-chain Amino Acids One-year After Sleeve Gastrectomy In Youth With Obesity And Its Association With Changes In Insulin Resistance

Abstract Disclosure: I. Becetti: None. M. Lauze: None. H. Lee: None. M. Bredella: None. M. Misra: None. V. Singhal: None. Introduction: Branched-chain amino acids (BCAAs), isoleucine, leucine and valine, have been linked to obesity, insulin resistance (IR) and risk for type 2 diabetes. Adults with obesity have a reduction in BCAA levels following metabolic and bariatric surgery (MBS), which may contribute to the modulation of metabolic advantages of MBS. We examine for the first time this relationship in youth with moderate-to-severe obesity who underwent sleeve gastrectomy (SG). Objective: To examine changes in dietary intake and serum BCAAs in youth with obesity one-year after SG, and their associations with changes in markers of IR. Methods: 53 youth 13-25 years old with severe obesity (41 females) were followed for a year; 25 had SG and 28 were non-surgical controls (NS). Subjects had fasting glucose and insulin levels and a 24-hour food recall. We assessed baseline and 12-month change within (Wilcoxon signed-rank test) and between (Student’s t-test/Wilcoxon Rank Sum test) groups, and associations between BCAAs and markers of IR (Spearman’s correlation). Results: SG and NS groups were similar for age, sex and race. SG had higher median body mass index (BMI) vs. NS at baseline [45.3 (42.1, 53.7) vs. 41.9 (38.4, 47.1) kg/m2; p=0.02]. At baseline, SG and NS did not differ for intake or serum levels of isoleucine, leucine, valine or total BCAAs. SG and NS groups also did not differ at baseline for glycated hemoglobin (HbA1C) or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, marker of IR). Over a year, SG vs. NS had greater reductions in BMI, serum isoleucine, leucine, valine and BCAAs (p≤0.02), and SG had significant within group reductions in intake of isoleucine, leucine, valine and BCAAs (p≤0.048). Further, SG vs. NS groups had greater reductions in HbA1c and HOMA-IR (p≤0.007). Serum BCAA levels were not associated with their dietary intake. Baseline HOMA-IR was positively associated with baseline serum levels of leucine (ρ=0.56, p=0.01). Over one year, decreases in HOMA-IR and HbA1c were positively associated with decreases in serum valine (ρ=0.60 and ρ=0.63, p=0.01 and p=0.007, respectively). Associations between changes in HOMA-IR and serum valine held after controlling for BMI (baseline and change) and dietary intake of valine. Conclusion: We demonstrate decreases in BCAA intake and serum levels one-year post-SG in youth with obesity. Associations between BCAAs and IR markers, even after controlling for BMI, suggest a potential role of BCAA in regulating metabolic health. Reducing serum levels of BCAAs may reduce IR. Presentation: Friday, June 16, 2023

Changes in Branched-Chain Amino Acids One Year after Sleeve Gastrectomy in Youth with Obesity and Their Association with Changes in Insulin Resistance.

Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13-24 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.