-
1.
Plasma Metabolomics Profile of "Insulin Sensitive" Male Hypogonadism after Testosterone Replacement Therapy.
Zolla, L, Ceci, M
International journal of molecular sciences. 2022;(3)
Abstract
Male hypogonadism is a disorder characterized by low levels of testosterone, but patients can either show normal insulin (insulin-sensitive (IS)) or over time they can become insulin-resistant (IR). Since the two groups showed different altered metabolisms, testosterone replacement therapy (TRT) could achieve different results. In this paper, we analyzed plasma from 20 IS patients with low testosterone (<8 nmol/L) and HOMAi < 2.5. The samples, pre- and post-treatment with testosterone for 60 days, were analyzed by UHPLC and mass spectrometry. Glycolysis was significantly upregulated, suggesting an improved glucose utilization. Conversely, the pentose phosphate pathway was reduced, while the Krebs cycle was not used. Branched amino acids and carnosine metabolism were positively influenced, while β-oxidation of fatty acids (FFA) was not activated. Cholesterol, HDL, and lipid metabolism did not show any improvements at 60 days but did so later in the experimental period. Finally, both malate and glycerol shuttle were reduced. As a result, both NADH and ATP were significantly lower. Interestingly, a significant production of lactate was observed, which induced the activation of the Cori cycle between the liver and muscles, which became the main source of energy for these patients without involving alanine. Thus, the treatment must be integrated with chemicals which are not restored in order to reactivate energy production.
-
2.
Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.
Ooi, DSQ, Ling, JQR, Sadananthan, SA, Velan, SS, Ong, FY, Khoo, CM, Tai, ES, Henry, CJ, Leow, MKS, Khoo, EYH, et al
The Journal of nutrition. 2021;(4):911-920
-
-
Free full text
-
Abstract
BACKGROUND Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. OBJECTIVE We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. METHODS A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group. RESULTS The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period. CONCLUSIONS BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.
-
3.
Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial.
Hernández-Conde, M, Llop, E, Gómez-Pimpollo, L, Fernández Carrillo, C, Rodríguez, L, Van Den Brule, E, Perelló, C, López-Gómez, M, Abad, J, Martínez-Porras, JL, et al
The American journal of gastroenterology. 2021;(11):2241-2249
Abstract
INTRODUCTION The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown. METHODS This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693). RESULTS Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091). DISCUSSION BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia.
-
4.
Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients.
Pinson, MR, Deutz, NEP, Harrykissoon, R, Zachria, AJ, Engelen, MPKJ
BMC pulmonary medicine. 2021;(1):351
Abstract
BACKGROUND Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. METHODS Seventy-eight outpatients with moderate to severe COPD (GOLD II-IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC-MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ < 0.05. RESULTS The COPD depressed (CD, n = 27) patients on average had mild depression, were obese (BMI: 31.7 [28.4, 34.9] kg/m2), and were characterized by shorter 6-min walk distance (P = 0.055), physical inactivity (P = 0.03), and poor quality of life (P = 0.01) compared to the non-depressed COPD (CN, n = 51) group. Lung function, disease history, body composition, cognitive performance, and daily protein intake were not different between the groups. In the CD group, plasma branched chain amino acid concentration (BCAA) was lower (P = 0.02), whereas leucine (P = 0.01) and phenylalanine (P = 0.003) clearance rates were higher. Reduced values were found for tyrosine plasma concentration (P = 0.005) even after adjustment for the large neutral amino acid concentration (= sum BCAA, tyrosine, phenylalanine and tryptophan) as a marker of dopamine synthesis (P = 0.048). CONCLUSION Mild depression in COPD is associated with poor daily performance and quality of life, and a set of metabolic changes in depressed COPD that include perturbation of large neutral amino acids, specifically the BCAAs. Trial registration clinicaltrials.gov: NCT01787682, 11 February 2013-Retrospectively registered; NCT02770092, 12 May 2016-Retrospectively registered; NCT02780219, 23 May 2016-Retrospectively registered; NCT03796455, 8 January 2019-Retrospectively registered.
-
5.
Branched-Chain Amino Acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study.
Tuccinardi, D, Perakakis, N, Farr, OM, Upadhyay, J, Mantzoros, CS
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3032-3036
-
-
Free full text
-
Abstract
BACKGROUND&AIMS: To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences. METHODS In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participated in two 5-day inpatient study admissions, during which they had a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts every morning. Between the two phases there was a 1-month washout period. RESULTS Fasting valine and isoleucine levels were reduced (p = .047 and p < .001) and beta-hydroxybutyrate levels were increased after 5-days of walnut consumption compared to placebo (p = .023). Fasting valine and isoleucine correlated with HOMA-IR while on walnut (r = 0.709, p = .032 and r = 0.679, p = .044). The postprandial area under the curve (AUC) of leucine in response to the smoothie consumption on day 5 was higher after walnut vs placebo (p = .023) and correlated negatively with the percentage of Kcal from carbohydrate and protein consumed during an ad libitum buffet meal consumed the same day for lunch (r = -0.661, p = .037; r = -0.628, p = .05, respectively). CONCLUSION The fasting and postabsorptive profiles of BCAAs are differentially affected by walnut consumption. The reduction in fasting valine and isoleucine may contribute to the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality, whereas the increase in postabsorptive profiles with walnuts may influence food preference. TRIAL REGISTRATION CLINICALTRIALS.GOV: Number: NCT02673281, Website: https://clinicaltrials.gov/ct2/show/NCT02673281.
-
6.
The use of BCAA to decrease delayed-onset muscle soreness after a single bout of exercise: a systematic review and meta-analysis.
Weber, MG, Dias, SS, de Angelis, TR, Fernandes, EV, Bernardes, AG, Milanez, VF, Jussiani, EI, de Paula Ramos, S
Amino acids. 2021;(11):1663-1678
Abstract
Branched-chain amino acids (BCAA) are used as a recovery method after exercise-induced muscle damage (EIMD). Although data suggest that BCAA may alleviate the delayed-onset muscle soreness (DOMS) evoked by EIMD, there is no consensus about the most effective supplementation protocol. To investigate the effects of BCAA on DOMS after a single exercise session that caused EIMD, a systematic review and meta-analysis were conducted on the effectiveness of BCAA supplementation to reduce DOMS symptoms in healthy subjects after a single session of EIMD. Randomized clinical trials (RCT) were searched in Medline, Cochrane Library, Science Direct, SciELO, LILACS, SciVerse Scopus, Springer Link journals, Wiley Online Library, and Scholar Google, until May 2021. Ten RCTs were included in the systematic review and nine in the meta-analysis. Seven studies demonstrated that BCAA reduced DOMS after 24 to 72 h. BCAA doses of up to 255 mg/kg/day, or in trained subjects, for mild to moderate EIMD, could blunt DOMS symptoms. However, high variability between studies due to training status, different doses, time of treatment, and severity of EIMD do not allow us to conclude whether BCAA supplementation is efficient in untrained subjects, applied acutely or during a period of pre to post days of EIMD, and at higher doses (> 255 mg/kg/day). The overall effects of BCAA on DOMS after a single session of exercise were considered useful for improving muscle recovery by reducing DOMS in trained subjects, at low doses, in mild to moderate EIMD, and should not be administered only after the EIMD protocol.
-
7.
Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.
Hiraiwa, H, Okumura, T, Kondo, T, Kato, T, Kazama, S, Kimura, Y, Ishihara, T, Iwata, E, Shimojo, M, Kondo, S, et al
Heart and vessels. 2021;(7):965-977
Abstract
Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer's ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer's ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93-365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan-Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer's ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.
-
8.
Branched-chain amino acid supplementation improves cycling performance in untrained cyclists.
Manaf, FA, Peiffer, JJ, Maker, GL, Fairchild, TJ
Journal of science and medicine in sport. 2021;(4):412-417
Abstract
OBJECTIVES To investigate the effects of acute branched-chain amino acid (BCAA) supplementation on cycling performance and neuromuscular fatigue during a prolonged, self-paced cycling time-trial. DESIGN Randomised double-blind counterbalanced crossover. METHODS Eighteen recreationally active men (mean±SD; age: 24.7±4.8 years old; body-weight, BW: 67.1±6.1kg; height: 171.7±4.9cm) performed a cycling time-trial on an electromagnetically-braked cycle ergometer. Participants were instructed to complete the individualised total work in the shortest time possible, while ingesting either BCAAs (pre-exercise: 0.084gkg-1 BW; during exercise: 0.056gkg-1h-1) or a non-caloric placebo solution. Rating of perceived exertion, power, cadence and heart rate were recorded throughout, while maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque using single and doublet stimulations were assessed at baseline, immediately post-exercise and 20-min post-exercise. RESULTS Supplementation with BCAA reduced (287.9±549.7s; p=0.04) time-to-completion and ratings of perceived exertion (p≤0.01), while concomitantly increasing heart rate (p=0.02). There were no between-group differences (BCAA vs placebo) in any of the neuromuscular parameters, but significant decreases (All p≤0.01) in maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque (single and doublet stimulations) were recorded immediately following the trial, and these did not recover to pre-exercise values by the 20min recovery time-point. CONCLUSIONS Compared to a non-caloric placebo, acute BCAA supplementation significantly improved performance in cycling time-trial among recreationally active individuals without any notable changes in either central or peripheral factors. This improved performance with acute BCAA supplementation was associated with a reduced rating of perceived exertion.
-
9.
Bariatric surgery reduces branched-chain amino acids' levels: a systematic review and meta-analysis.
Barati-Boldaji, R, Esmaeilinezhad, Z, Babajafari, S, Kazemi, A, Clark, CCT, Mazidi, M, Ofori-Asenso, R, Haghighat, N, Shafiee, M, Mazloomi, SM
Nutrition research (New York, N.Y.). 2021;:80-90
Abstract
Bariatric surgery is a metabolic surgery known to be an efficient treatment for weight loss, with adequate long-term maintenance. Interestingly, some studies have reported a reduction in branched chained amino acids (BCAAs) after bariatric surgery, which putatively contributes to post-surgical metabolic improvement. The current systematic review and meta-analysis investigated the effect of bariatric surgery on the level of BCAAs. PubMed, SCOPUS, EMBASE, and Web of Science databases were searched from their inception to July 2019. All clinical trials which investigated the effect of bariatric surgery on the levels of valine, leucine, and isoleucine, for more than one week, were included. Nine studies (11 effect sizes) were analyzed via meta-analytical techniques using random-effects models. The pooled data suggested that bariatric surgery significantly reduced the valine (standardized mean difference [SMD]: -1.89, 95% confidence interval [CI]: -2.79, -0.99, I2 = 90.9%), leucine (SMD: -0.96, 95% CI: -1.48, -0.44, I2 = 72.4%), and isoleucine (SMD: -0.58, 95% CI: -0.84, -0.31, I2 = 66.3%) levels after surgery compared with before the surgery. Overall, bariatric surgery significantly reduced the levels of valine, leucine, and isoleucine compared with before the surgery. Further large-scale and homogenous trials are needed to better discern the generalizability of our findings.
-
10.
Amino acid differences between diabetic older adults and non-diabetic older adults and their associations with cardiovascular function.
Kovalik, JP, Zhao, X, Gao, F, Leng, S, Chow, V, Chew, H, Teo, LLY, Tan, RS, Ewe, SH, Tan, HC, et al
Journal of molecular and cellular cardiology. 2021;:63-71
Abstract
BACKGROUND Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function. METHODS In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination. RESULTS We studied a total of 515 participants (women 50%, n = 255) with a mean age 73 (SD = 4.3) years. Diabetics had higher alanine (562 vs 448, p < 0.0001), higher glutamate (107 vs 95, p = 0.016), higher proline (264 vs 231, p = 0.008) and lower arginine (107 vs 117, p = 0.043), lower citrulline (30 vs 38, p = 0.006) levels (μM) compared to non-diabetics. Over time, changes in amino acid profiles differentiated diabetic older adults from non-diabetic older adults, with greater accumulation of alanine (p = 0.002), proline (p = 0.008) and (non-significant) trend towards greater accumulation of glycine (p = 0.057) among the older diabetics compared to the older non-diabetics. However, independent of diabetes status, amino acids were associated with cardiovascular functions in ageing, [archived valine (p = 0.011), leucine (p = 0.011), archived isoleucine (p = 0.0006), archived serine (p = 0.008), archived glycine (p = 0.006) methionine (p = 0.003)] which were associated with impairments in E/A ratio. CONCLUSION Markers of branched chain amino acids and one ‑carbon metabolism pathways were associated with changes in cardiovascular function in older adults regardless of diabetes status. However, nitrogen handling pathways were specifically altered among older adults with diabetes. These findings broaden our understanding into specific amino acid pathways that may be altered between diabetic and non-diabetic older adults, and their relevance to cardiovascular function in ageing. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02791139.