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1.
Plasma branched chain amino acids are lower in short-term profound hypothyroidism and increase in response to thyroid hormone supplementation.
van der Boom, T, Gruppen, EG, Lefrandt, JD, Connelly, MA, Links, TP, Dullaart, RPF
Scandinavian journal of clinical and laboratory investigation. 2020;(7):562-566
Abstract
Branched chain amino acids (BCAA) are implicated in the pathogenesis of cardiometabolic diseases conceivably by affecting insulin resistance and mitochondrial dysfunction. Circulating BCAA levels may predict (subclinical) atherosclerosis, diabetes and hypertension development but the factors involved in BCAA regulation are incompletely understood. Given the key role of thyroid hormones on many metabolic processes including protein metabolism, we aimed to determine effects of thyroid dysfunction on circulating BCAA. Effects of short-term profound hypothyroidism on plasma BCAA were determined in 17 patients who had undergone total thyroidectomy for differentiated thyroid carcinoma. Patients were studied during hypothyroidism, i.e. after thyroidectomy, and after thyroid hormone supplementation. Plasma BCAA (sum of valine, leucine and isoleucine) and alanine were measured by nuclear magnetic resonance spectroscopy. During hypothyroidism (median thyroid-stimulating hormone 81 (IQR 67-120.5) mU/L), plasma BCAA were lower (255 (IQR 222-289) µmol/L) compared to a euthyroid reference population (n = 5579; 377 µmol/L (2.5th to 97.5th percentile 258-548), p < 0.001). After 20 weeks of thyroid hormone supplementation (thyroid-stimulating hormone 0.03 (IQR 0.01-0.14 mU/L) plasma BCAA had increased (328 (IQR 272-392) µmol/L, p = .001), but plasma alanine concentrations were unaltered (p = .50). Changes in body weight in response to thyroid hormone supplementation were correlated with changes in plasma BCAA (r = 0.721 p = .001, but not with changes in cholesterol or glucose (p > .80). In conclusion, plasma BCAA concentrations are lower during short-term profound hypothyroidism in humans, and increase in response to thyroid hormone supplementation. Changes in BCAA and in body weight after reversal of the hypothyroid state appear to be interrelated.
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2.
Plasma BCAA Changes in Patients With NAFLD Are Sex Dependent.
Grzych, G, Vonghia, L, Bout, MA, Weyler, J, Verrijken, A, Dirinck, E, Chevalier Curt, MJ, Van Gaal, L, Paumelle, R, Francque, S, et al
The Journal of clinical endocrinology and metabolism. 2020;(7)
Abstract
CONTEXT Plasma branched chain amino acid (BCAA) concentrations correlate positively with body mass index (BMI), measures of insulin resistance (IR), and severity of nonalcoholic fatty liver disease (NAFLD). Moreover, plasma BCAA concentrations also differ between the sexes, which display different susceptibilities to cardio-metabolic diseases. OBJECTIVE Assess whether plasma BCAA concentrations associate with NAFLD severity independently of BMI, IR, and sex. PATIENTS Patients visiting the obesity clinic of the Antwerp University Hospital were consecutively recruited from 2006 to 2014. DESIGN AND SETTING A cross-sectional study cohort of 112 obese patients (59 women and 53 men) was divided into 4 groups according to NAFLD severity. Groups were matched for sex, age, BMI, homeostatic model assessment of IR, and hemoglobin A1c. MAIN OUTCOME MEASURES Fasting plasma BCAA concentrations were measured by tandem mass spectrometry using the aTRAQ™ method. RESULTS In the study cohort, a modest positive correlation was observed between plasma BCAA concentrations and NAFLD severity, as well as a strong effect of sex on plasma BCAA levels. Subgroup analysis by sex revealed that while plasma BCAA concentrations increased with severity of NAFLD in women, they tended to decrease in men. Additionally, only women displayed significantly increased plasma BCAAs with increasing fibrosis. CONCLUSION Plasma BCAA concentrations display sex-dimorphic changes with increasing severity of NAFLD, independently of BMI, IR, and age. Additionally, plasma BCAA are associated with significant fibrosis in women, but not in men. These results highlight the importance of a careful consideration of sex as a major confounding factor in cross-sectional studies of NAFLD.
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3.
Associations between Plasma Branched Chain Amino Acids and Health Biomarkers in Response to Resistance Exercise Training Across Age.
Sayda, MH, Phillips, BE, Williams, JP, Greenhaff, PL, Wilkinson, DJ, Smith, K, Atherton, PJ
Nutrients. 2020;(10)
Abstract
Leucine, isoleucine and valine (i.e., the branched chain amino acids, BCAA) play a key role in the support and regulation of tissue protein regulation and also as energy substrates. However, positive relationships exist between elevated levels of BCAA and insulin resistance (IR). Thus, we sought to investigate the links between fasting plasma BCAA following a progressive resistance exercise training (RET) programme, an intervention known to improve metabolic health. Fasting plasma BCAA were quantified in adults (young: 18-28 y, n = 8; middle-aged: 45-55 y, n = 9; older: 65-75 y, n = 15; BMI: 23-28 kg/m2, both males and females (~50:50), in a cross-sectional, intervention study. Participants underwent 20-weeks whole-body RET. Measurements of body composition, muscle strength (1-RM) and metabolic health biomarkers (e.g., HOMA-IR) were made pre- and post-RET. BCAA concentrations were determined by gas-chromatography mass spectrometry (GC-MS). No associations were observed across age with BCAA; however, RET elicited (p < 0.05) increases in plasma BCAA (all age-groups), while HOMA-IR scores reduced (p < 0.05) following RET. After RET, positive correlations in lean body mass (p = 0.007) and strength gains (p = 0.001) with fasting BCAA levels were observed. Elevated BCAA are not a robust marker of ageing nor IR in those with a healthy BMI; rather, despite decreasing IR, RET was associated with increased BCAA.
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4.
Emerging Roles for Branched-Chain Amino Acid Metabolism in Cancer.
Sivanand, S, Vander Heiden, MG
Cancer cell. 2020;(2):147-156
Abstract
Metabolic pathways must be adapted to support cell processes required for transformation and cancer progression. Amino acid metabolism is deregulated in many cancers, with changes in branched-chain amino acid metabolism specifically affecting cancer cell state as well as systemic metabolism in individuals with malignancy. This review highlights key concepts surrounding the current understanding of branched-chain amino acid metabolism and its role in cancer.
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5.
Branched Chain Amino Acids, Cardiometabolic Risk Factors and Outcomes in Older Men: The Concord Health and Ageing in Men Project.
Le Couteur, DG, Ribeiro, R, Senior, A, Hsu, B, Hirani, V, Blyth, FM, Waite, LM, Simpson, SJ, Naganathan, V, Cumming, RG, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(10):1805-1810
Abstract
Increased blood levels of branched chain amino acids (BCAAs) have been associated with cardiometabolic risk factors. Here, we studied 918 community-dwelling older men to determine the relationship between BCAAs and other amino acids with cardiometabolic risk factors, major cardiovascular endpoints (MACE), and mortality. BCAAs had robust associations with many adverse metabolic risk factors (increased glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), triglycerides; decreased high-density lipoprotein cholesterol). However, paradoxically, participants with lower levels of BCAAs had greater mortality and MACE possibly because increasing age and frailty, both of which were associated with lower BCAA levels, are powerful risk factors for these outcomes in older people. Overall, amino acids that were lowest in frail subjects (BCAAs, α-aminobutyric acid [AABA], histidine, lysine, methionine, threonine, tyrosine) were inversely associated with mortality and MACE. In conclusion, BCAAs are biomarkers for important outcomes in older people including cardiometabolic risk factors, frailty, and mortality. In old age, frailty becomes a dominant risk factor for MACE and mortality.
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6.
Short-term branched-chain amino acid supplementation does not enhance vertical jump in professional volleyball players. A double-blind, controlled, randomized study.
Martín-Martínez, JP, Calleja Gonzalez, J, Adsuar Sala, JC, Gómez-Pomares, S, Carlos-Vivas, J, Pérez-Gómez, J
Nutricion hospitalaria. 2020;(5):1007-1011
Abstract
To the best of the authors' knowledge, no previous studies have described the effect of branched-chain amino acids (BCAA) on vertical performance during a week in professional volleyball players. This study assessed BCAA supplementation for a week, aiming to improve vertical jump performance in male professional volleyball players. Twelve male volleyballers were randomly assigned to a BCAA group (n = 6) or a control group (n = 6). The BCAA group ingested 21 g over a week, 7 g per day on Monday, Wednesday, and Friday, before a volleyball training session, while the control group drank a placebo drink. Participants performed 8 maximal countermovement jumps (CMJ); the 3 CMJs on Monday and Wednesday were evaluated after warm-up, after plyometric training, and at the end of the training session; and the 2 CMJs on Friday were evaluated after warm-up, and at the end of the training session. Compared with baseline, no significant differences in CMJ over the week were observed in BCAA or control group, neither between groups. The results indicated that 21 g of BCAA supplementation over a week did not improve vertical jump performance in professional volleyball players.
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7.
Why Are Branched-Chain Amino Acids Increased in Starvation and Diabetes?
Holeček, M
Nutrients. 2020;(10)
Abstract
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are increased in starvation and diabetes mellitus. However, the pathogenesis has not been explained. It has been shown that BCAA catabolism occurs mostly in muscles due to high activity of BCAA aminotransferase, which converts BCAA and α-ketoglutarate (α-KG) to branched-chain keto acids (BCKAs) and glutamate. The loss of α-KG from the citric cycle (cataplerosis) is attenuated by glutamate conversion to α-KG in alanine aminotransferase and aspartate aminotransferase reactions, in which glycolysis is the main source of amino group acceptors, pyruvate and oxaloacetate. Irreversible oxidation of BCKA by BCKA dehydrogenase is sensitive to BCKA supply, and ratios of NADH to NAD+ and acyl-CoA to CoA-SH. It is hypothesized that decreased glycolysis and increased fatty acid oxidation, characteristic features of starvation and diabetes, cause in muscles alterations resulting in increased BCAA levels. The main alterations include (i) impaired BCAA transamination due to decreased supply of amino groups acceptors (α-KG, pyruvate, and oxaloacetate) and (ii) inhibitory influence of NADH and acyl-CoAs produced in fatty acid oxidation on citric cycle and BCKA dehydrogenase. The studies supporting the hypothesis and pros and cons of elevated BCAA concentrations are discussed in the article.
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8.
The Effects of Timing of a Leucine-Enriched Amino Acid Supplement on Body Composition and Physical Function in Stroke Patients: A Randomized Controlled Trial.
Ikeda, T, Morotomi, N, Kamono, A, Ishimoto, S, Miyazawa, R, Kometani, S, Sako, R, Kaneko, N, Iida, M, Kawate, N
Nutrients. 2020;(7)
Abstract
The combination of exercise and nutritional intervention is widely used for stroke patients, as well as frail or sarcopenic older persons. As previously shown, supplemental branched chain amino acids (BCAAs) or protein to gain muscle mass has usually been given just after exercise. This study investigated the effect of the timing of supplemental BCAAs with exercise intervention on physical function in stroke patients. The participants were randomly assigned to two groups based on the timing of supplementation: breakfast (n = 23) and post-exercise (n = 23). The supplement in the breakfast group was provided at 08:00 with breakfast, and in the post-exercise group it was provided just after the exercise session in the afternoon at 14:00-18:00. In both groups, the exercise intervention was performed with two sessions a day for two months. The main effects were observed in body fat mass (p = 0.02, confidence interval (CI): 13.2-17.7), leg press strength (p = 0.04, CI: 94.5-124.5), and Berg balance scale (p = 0.03, CI: 41.6-52.6), but no interaction with intake timing was observed. Although the effect of the timing of supplementation on skeletal muscle mass was similar in both groups, BCAA intake with breakfast was effective for improving physical performance and decreasing body fat mass. The results suggest that a combination of BCAA intake with breakfast and an exercise program was effective for promoting rehabilitation of post-stroke patients.
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9.
Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.
Park, JG, Tak, WY, Park, SY, Kweon, YO, Chung, WJ, Jang, BK, Bae, SH, Lee, HJ, Jang, JY, Suk, KT, et al
Nutrients. 2020;(5)
Abstract
BACKGROUND AND AIMS Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. METHODS Liver cirrhosis patients with Child-Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. RESULTS A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221-0.684, p < 0.001). CONCLUSION Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.
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10.
Circulating branched-chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register.
Lim, LL, Lau, ESH, Fung, E, Lee, HM, Ma, RCW, Tam, CHT, Wong, WKK, Ng, ACW, Chow, E, Luk, AOY, et al
Diabetes/metabolism research and reviews. 2020;(3):e3253
Abstract
AIM: Levels of branched-chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown. METHODS In this prospective observational study, we measured BCAAs in fasting serum samples collected at inception from 2139 T2D patients free of cardiovascular-renal diseases. The study outcome was the first hospitalization for HF. RESULTS During 29 103 person-years of follow-up, 115 primary events occurred (age: 54.8 ± 11.2 years, 48.2% men, median [interquartile range] diabetes duration: 5 years [1-10]). Patients with incident HF had 5.6% higher serum BCAAs than those without HF (median 639.3 [561.3-756.3] vs 605.2 [524.8-708.7] μmol/L; P = .01). Serum BCAAs had a positive linear association with incident HF (per-SD increase in logarithmically transformed BCAAs: hazard ratio [HR] 1.22 [95% CI 1.07-1.39]), adjusting for age, sex, and diabetes duration. The HR remained significant after sequential adjustment of risk factors including incident coronary heart disease (1.24, 1.09-1.41); blood pressure, low-density lipoprotein cholesterol, and baseline use of related medications (1.31, 1.14-1.50); HbA1c , waist circumference, triglyceride, and baseline use of related medications (1.28, 1.11-1.48); albuminuria and estimated glomerular filtration rate (1.28, 1.11-1.48). The competing risk of death analyses showed similar results. CONCLUSIONS Circulating levels of BCAAs are independently associated with incident HF in patients with T2D. Prospective cohort analysis and randomized trials are needed to evaluate the long-term safety and efficacy of using different interventions to optimize BCAAs levels in these patients.